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Build-up of venom immunotherapy which
schedule is the best
Dario Antolin-Amerigo
Hospital Universitario Priacutencipe de AsturiasAlcalaacute de Henares Madrid
Spain
Conflicts of Interest
I declare no conflicts of interest
Build-up of VIT
bull A model for the efficacy and reliability of allergen immunotherapy
bull A great deal of protocols bull Comparison challenging heterogeneity (variables amp
methods)
SlowWeekly
Rush3-7 days
UltrarushHours-2 days
15-30 minute intervals
Background Tailor-madeEfficacy amp Tolerance
Pretreatment ConclusionsExtracts
Build-up of VIT
Patient
MedicalFactors
Logistic
OtherFactors
Financial
Extract
Purified
Non Purified
Depot
Pretreatment
Antihistamines
Omalizumab
Montelukast
Others
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Pretreatment
Extract
Patient
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Rush VIT by Sturm et al (60 min)6
Day 1 Day 2 Day 3 Day 4
0001 08 8 80
001 10 10 100
01 20 20
02 40 40
04 60 60
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
079 Bee012 Vespid
=
Sturm G Kraumlnke B Rudolph C Aberer W Rush Hymenoptera venom immunotherapy a safe and practical protocol for high-risk patients J Allergy Clin Immunol 2002 Dec110(6)928-33
1 High risk of future severe reactions case history and test results
2 High risk for side effects of venom immunotherapy (elderly persons with coexisting internal disease)
3 Need protection soon
4 Rural areas
5 Highly sensitized and anxious
6 Highly sensitized children
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Sturm G Kraumlnke B Rudolph C Aberer W Rush Hymenoptera venom immunotherapy a safe and practical protocol for high-risk patients J Allergy Clin Immunol 2002 Dec110(6)928-33
Day
Venom
concentration
mcgmL
Volume mL Dose mcg
Daily
accumulative
dose mcg
1
1 005 005
1 01 01
1 02 02
1 04 04
1 08 08
10 02 2
10 05 5
10 10 10
100 02 20
100 02 20 5855
2
100 02 20
100 03 30
100 05 50 100
3 100 10 100 100
There were 15-min intervals between venom injections
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Goldberg A Confino-Cohen R Rush venom immunotherapy
in patients experiencing recurrent systemic reactions
to conventional venom immunotherapy Ann Allergy
Asthma Immunol 2003 Oct91(4)405-10
The Bonn Rush VIT protocol (100000 SQ-E=100 mcg insect venom)
Day Preparation Concentration(mcgmL) Volume (mL) Dose (mcg)
1 (Monday) Lyophilisate 0000001 02 00000002
000001 02 0000002
00001 02 000002
0001 02 00002
2 (Tuesday) Lyophilisate 001 02 0002
001 04 0004
001 08 0008
01 02 002
3 (Wednesday)
Lyophilisate 01 04 004
01 08 008
1 02 02
1 04 04
4 (Thursday) Lyophilisate 1 08 08
10 02 02
10 04 04
10 08 08
5 (Friday) Lyophilisate 100 02 20
100 03 30
100 04 40
100 05 50
6 (Monday) Lyophilisate 100 06 60
100 07 70
100 08 80
7 (Tuesday) LyophilisateDepot
100 09 90
100 1 100
Total Dose 55555
Build-up of VIT
Wenzel J Meissner-Kraemer M Bauer R Bieber T Gerdsen R Safety of rush insect venom
immunotherapy The results of a retrospective study in 178 patients Allergy 2003
Nov58(11)1176-9
179 SRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Wenzel J Meissner-Kraemer M Bauer R Bieber T Gerdsen R Safety of rush insect venom
immunotherapy The results of a retrospective study in 178 patients Allergy 2003
Nov58(11)1176-9
179 SRs
210 min Ultra-rush Protocol4
Day Time Injected
venom (mcgr)
1
0 h 01
30 min 1
1 h 10
15 h 20
25 h 30
35 h 40
150 50
30 min 50
45 One injection of 100 mcgr
Monthly One injection of 100 mcgr
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SRs1279
HBV 30gtYJV 32
Birnbaum J Ramadour M Magnan A Vervloet D Hymenoptera ultra-rush venom immunotherapy (210 min) a safety study and risk factors Clin Exp Allergy 2003 Jan33(1)58-64
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brehler R Wolf H Kuumltting B Schnitker J Luger TSafety of a two-day ultrarush insect venom immunotherapy protocol in comparison with protocols of longer duration and involving a larger number of injections J Allergy Clin Immunol
2000 Jun105(6 Pt 1)1231-5
212 adverse
reactions
darrSRharr darr Injections
Day Dose ml administered Mcgr administered Conc mcgml
1
1 010 001 01
2 010 01 1
3 010 1 10
4 020 2 10
2
5 030 3 10
6 035 35 10
7 035 35 10
3
8 010 10 100
9 015 15 100
10 015 15 100
4
11 020 20 100
12 025 25 100
13 025 25 100
5
14 030 30 100
15 035 35 100
16 035 35 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Bilograve MB Cinti B Brianzoni MF Braschi MC Bonifazi M Antonicelli LHoneybee venom immunotherapy a comparative study using purified and nonpurified aqueous extracts in patients with normal Basal serum tryptase concentrations J
Allergy (Cairo) 20122012869243
NPA275
PA25
Day DoseMcg
administeredinterval
1
1 01 30 min
2 1 30 min
3 10 30 min
4 20 30 min
5 30 60 min
6 50 60 min
7 7 100
14 8 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Roll A Hofbauer G Ballmer-Weber BK Schmid-Grendelmeier P Safety of specific immunotherapy using a four-hour ultra-rush induction scheme in bee and wasp allergy J
Investig Allergol Clin Immunol 200616(2)79-85
Injection
numberDose (mcg) Interval (min)
1 01 30
2 1 30
3 10 30
4 20 60
5 30 60
6 50 180
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Koumlhli-Wiesner A Stahlberger L Bieli C Stricker T Lauener R Induction of specific immunotherapy with hymenoptera venoms using ultrarush regimen in children safety and tolerance J Allergy (Cairo) 20122012790910
SR 29
SR 12
Ultrarush initiation
Visit 1
At 30 min intervals 01 mcg 1 mcg 3 mcg 10
mcg 20 mcg 30 mcg then
For those allocated the 50-target no more
doses on day 1
For those allocated the 100 mcg target delay
60 min and give 40 mcg
Visit 2
At 20 min intervals
For those allocated the 50-target 25 mcg + 25
mcg
For those allocated the 100-target 50 mcg + 50
mcg
Visit 3 Maintenance dose 50 mcg or 100 mcg
Semirush initiation
Visit 1At 20 min intervals 00001 mcg 0001 mcg
001 mcg
Visit 2 At 20 min intervals 001 01 mcg 03 mcg
Visit 3 At 30 min interval 03mcg 1mcg 3 mcg
Visit 4 At 30 min interval 3mcg 10 mcg
Visit 5 At 30 min interval 10mcg 20 mcg
Visit 6 At 30 min interval 20 mcg 30 mcg
Visit 7For those allocated the 50 mcg target (30 min
interval) 25 mcg 25 mcg
For those allocated the 100mcg (30 min
interval)30 mcg 40 mcg
Visit 8 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval) 50mcg 50 mcg
Visit 9 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval)70 mcg 30 mcg
Visit 10 Maintenance dose 50 mcg or 100 mcg
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
injections
LLR SR
Group A 199 0
Group B 32 09
Group C 36 056
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Patella V Florio G Giuliano A et al Hymenoptera Venom Immunotherapy Tolerance and Efficacy of an UltrarushProtocol versus a Rush and a Slow Conventional Protocol J Allergy (Cairo)20122012192192
P=027
3 Days Rush VIT
Day 1
1mcgmL
10 mcgmL
100 mcgmL
005 01 02 04 08 mL (005 01 02 04 08
mcg)
02 05 1 mL (2 5 10 mcg)
02 02 mL (20 20 mcg)
Day 2
100 mcgmL 02 03 05 mL (20 30 50 mcg)
Day 3
100 mcgmL 1 mL (100 mcg)
Conventional Regimen
1 mcgmL005 01 02 04 mL (005 01
02 04 mcg)
10 mcgmL005 01 02 04 mL (05 1 2 4
mcg)
100 mcgmL
002 005 007 01 02 04
06 08 1 ml (2 5 7 10 20 40
60 80 100 mcg)
Build-up of VIT
Goldberg A Yogev A Confino-Cohen R Three Days Rush Venom Immunotherapy in Bee Allergy Safe Inexpensive and
Instantaneously Effective Int Arch Allergy Immunol201115690-98
296 SRs
(BeegtV)
208SR
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Day Vial Volume (mL) Dosis (mcg)
1
1 01 01
1 02 02
1 04 04
1 08 08
2 02 2
2
2 04 4
2 08 8
3 01 10
3 02 20
3
3 04 40
3 06 60
3 08 80
3 1 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
48 patients
25 LR
2 patients mild SR
Saacutenchez-Morillas L Reantildeo Martos M Rodriacuteguez Mosquera M Iglesias Cadarso A Domiacutenguez Laacutezaro AR Safety of rushimmunotherapy with Hymenoptera venom Allergol Immunopathol (Madr) 200533(4)224-7 Spanish
Vial 1=1 mcgmLVial 2=10 mcgmL
Vial 3=100 mcgmL
Dose administered
(mcg)Time (min)
01 0
1 30
10 60
20 90
30 120
40 150
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Schiavino D Nucera E Pollastrini E De Pasquale T Buonomo A Bartolozzi F Lombardo C Roncallo C Patriarca G Specific ultrarush desensitization in Hymenoptera venom-allergic patients Ann Allergy Asthma Immunol 2004
Apr92(4)409-13
7 mildSRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Conflicts of Interest
I declare no conflicts of interest
Build-up of VIT
bull A model for the efficacy and reliability of allergen immunotherapy
bull A great deal of protocols bull Comparison challenging heterogeneity (variables amp
methods)
SlowWeekly
Rush3-7 days
UltrarushHours-2 days
15-30 minute intervals
Background Tailor-madeEfficacy amp Tolerance
Pretreatment ConclusionsExtracts
Build-up of VIT
Patient
MedicalFactors
Logistic
OtherFactors
Financial
Extract
Purified
Non Purified
Depot
Pretreatment
Antihistamines
Omalizumab
Montelukast
Others
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Pretreatment
Extract
Patient
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Rush VIT by Sturm et al (60 min)6
Day 1 Day 2 Day 3 Day 4
0001 08 8 80
001 10 10 100
01 20 20
02 40 40
04 60 60
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
079 Bee012 Vespid
=
Sturm G Kraumlnke B Rudolph C Aberer W Rush Hymenoptera venom immunotherapy a safe and practical protocol for high-risk patients J Allergy Clin Immunol 2002 Dec110(6)928-33
1 High risk of future severe reactions case history and test results
2 High risk for side effects of venom immunotherapy (elderly persons with coexisting internal disease)
3 Need protection soon
4 Rural areas
5 Highly sensitized and anxious
6 Highly sensitized children
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Sturm G Kraumlnke B Rudolph C Aberer W Rush Hymenoptera venom immunotherapy a safe and practical protocol for high-risk patients J Allergy Clin Immunol 2002 Dec110(6)928-33
Day
Venom
concentration
mcgmL
Volume mL Dose mcg
Daily
accumulative
dose mcg
1
1 005 005
1 01 01
1 02 02
1 04 04
1 08 08
10 02 2
10 05 5
10 10 10
100 02 20
100 02 20 5855
2
100 02 20
100 03 30
100 05 50 100
3 100 10 100 100
There were 15-min intervals between venom injections
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Goldberg A Confino-Cohen R Rush venom immunotherapy
in patients experiencing recurrent systemic reactions
to conventional venom immunotherapy Ann Allergy
Asthma Immunol 2003 Oct91(4)405-10
The Bonn Rush VIT protocol (100000 SQ-E=100 mcg insect venom)
Day Preparation Concentration(mcgmL) Volume (mL) Dose (mcg)
1 (Monday) Lyophilisate 0000001 02 00000002
000001 02 0000002
00001 02 000002
0001 02 00002
2 (Tuesday) Lyophilisate 001 02 0002
001 04 0004
001 08 0008
01 02 002
3 (Wednesday)
Lyophilisate 01 04 004
01 08 008
1 02 02
1 04 04
4 (Thursday) Lyophilisate 1 08 08
10 02 02
10 04 04
10 08 08
5 (Friday) Lyophilisate 100 02 20
100 03 30
100 04 40
100 05 50
6 (Monday) Lyophilisate 100 06 60
100 07 70
100 08 80
7 (Tuesday) LyophilisateDepot
100 09 90
100 1 100
Total Dose 55555
Build-up of VIT
Wenzel J Meissner-Kraemer M Bauer R Bieber T Gerdsen R Safety of rush insect venom
immunotherapy The results of a retrospective study in 178 patients Allergy 2003
Nov58(11)1176-9
179 SRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Wenzel J Meissner-Kraemer M Bauer R Bieber T Gerdsen R Safety of rush insect venom
immunotherapy The results of a retrospective study in 178 patients Allergy 2003
Nov58(11)1176-9
179 SRs
210 min Ultra-rush Protocol4
Day Time Injected
venom (mcgr)
1
0 h 01
30 min 1
1 h 10
15 h 20
25 h 30
35 h 40
150 50
30 min 50
45 One injection of 100 mcgr
Monthly One injection of 100 mcgr
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SRs1279
HBV 30gtYJV 32
Birnbaum J Ramadour M Magnan A Vervloet D Hymenoptera ultra-rush venom immunotherapy (210 min) a safety study and risk factors Clin Exp Allergy 2003 Jan33(1)58-64
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brehler R Wolf H Kuumltting B Schnitker J Luger TSafety of a two-day ultrarush insect venom immunotherapy protocol in comparison with protocols of longer duration and involving a larger number of injections J Allergy Clin Immunol
2000 Jun105(6 Pt 1)1231-5
212 adverse
reactions
darrSRharr darr Injections
Day Dose ml administered Mcgr administered Conc mcgml
1
1 010 001 01
2 010 01 1
3 010 1 10
4 020 2 10
2
5 030 3 10
6 035 35 10
7 035 35 10
3
8 010 10 100
9 015 15 100
10 015 15 100
4
11 020 20 100
12 025 25 100
13 025 25 100
5
14 030 30 100
15 035 35 100
16 035 35 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Bilograve MB Cinti B Brianzoni MF Braschi MC Bonifazi M Antonicelli LHoneybee venom immunotherapy a comparative study using purified and nonpurified aqueous extracts in patients with normal Basal serum tryptase concentrations J
Allergy (Cairo) 20122012869243
NPA275
PA25
Day DoseMcg
administeredinterval
1
1 01 30 min
2 1 30 min
3 10 30 min
4 20 30 min
5 30 60 min
6 50 60 min
7 7 100
14 8 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Roll A Hofbauer G Ballmer-Weber BK Schmid-Grendelmeier P Safety of specific immunotherapy using a four-hour ultra-rush induction scheme in bee and wasp allergy J
Investig Allergol Clin Immunol 200616(2)79-85
Injection
numberDose (mcg) Interval (min)
1 01 30
2 1 30
3 10 30
4 20 60
5 30 60
6 50 180
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Koumlhli-Wiesner A Stahlberger L Bieli C Stricker T Lauener R Induction of specific immunotherapy with hymenoptera venoms using ultrarush regimen in children safety and tolerance J Allergy (Cairo) 20122012790910
SR 29
SR 12
Ultrarush initiation
Visit 1
At 30 min intervals 01 mcg 1 mcg 3 mcg 10
mcg 20 mcg 30 mcg then
For those allocated the 50-target no more
doses on day 1
For those allocated the 100 mcg target delay
60 min and give 40 mcg
Visit 2
At 20 min intervals
For those allocated the 50-target 25 mcg + 25
mcg
For those allocated the 100-target 50 mcg + 50
mcg
Visit 3 Maintenance dose 50 mcg or 100 mcg
Semirush initiation
Visit 1At 20 min intervals 00001 mcg 0001 mcg
001 mcg
Visit 2 At 20 min intervals 001 01 mcg 03 mcg
Visit 3 At 30 min interval 03mcg 1mcg 3 mcg
Visit 4 At 30 min interval 3mcg 10 mcg
Visit 5 At 30 min interval 10mcg 20 mcg
Visit 6 At 30 min interval 20 mcg 30 mcg
Visit 7For those allocated the 50 mcg target (30 min
interval) 25 mcg 25 mcg
For those allocated the 100mcg (30 min
interval)30 mcg 40 mcg
Visit 8 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval) 50mcg 50 mcg
Visit 9 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval)70 mcg 30 mcg
Visit 10 Maintenance dose 50 mcg or 100 mcg
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
injections
LLR SR
Group A 199 0
Group B 32 09
Group C 36 056
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Patella V Florio G Giuliano A et al Hymenoptera Venom Immunotherapy Tolerance and Efficacy of an UltrarushProtocol versus a Rush and a Slow Conventional Protocol J Allergy (Cairo)20122012192192
P=027
3 Days Rush VIT
Day 1
1mcgmL
10 mcgmL
100 mcgmL
005 01 02 04 08 mL (005 01 02 04 08
mcg)
02 05 1 mL (2 5 10 mcg)
02 02 mL (20 20 mcg)
Day 2
100 mcgmL 02 03 05 mL (20 30 50 mcg)
Day 3
100 mcgmL 1 mL (100 mcg)
Conventional Regimen
1 mcgmL005 01 02 04 mL (005 01
02 04 mcg)
10 mcgmL005 01 02 04 mL (05 1 2 4
mcg)
100 mcgmL
002 005 007 01 02 04
06 08 1 ml (2 5 7 10 20 40
60 80 100 mcg)
Build-up of VIT
Goldberg A Yogev A Confino-Cohen R Three Days Rush Venom Immunotherapy in Bee Allergy Safe Inexpensive and
Instantaneously Effective Int Arch Allergy Immunol201115690-98
296 SRs
(BeegtV)
208SR
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Day Vial Volume (mL) Dosis (mcg)
1
1 01 01
1 02 02
1 04 04
1 08 08
2 02 2
2
2 04 4
2 08 8
3 01 10
3 02 20
3
3 04 40
3 06 60
3 08 80
3 1 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
48 patients
25 LR
2 patients mild SR
Saacutenchez-Morillas L Reantildeo Martos M Rodriacuteguez Mosquera M Iglesias Cadarso A Domiacutenguez Laacutezaro AR Safety of rushimmunotherapy with Hymenoptera venom Allergol Immunopathol (Madr) 200533(4)224-7 Spanish
Vial 1=1 mcgmLVial 2=10 mcgmL
Vial 3=100 mcgmL
Dose administered
(mcg)Time (min)
01 0
1 30
10 60
20 90
30 120
40 150
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Schiavino D Nucera E Pollastrini E De Pasquale T Buonomo A Bartolozzi F Lombardo C Roncallo C Patriarca G Specific ultrarush desensitization in Hymenoptera venom-allergic patients Ann Allergy Asthma Immunol 2004
Apr92(4)409-13
7 mildSRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Build-up of VIT
bull A model for the efficacy and reliability of allergen immunotherapy
bull A great deal of protocols bull Comparison challenging heterogeneity (variables amp
methods)
SlowWeekly
Rush3-7 days
UltrarushHours-2 days
15-30 minute intervals
Background Tailor-madeEfficacy amp Tolerance
Pretreatment ConclusionsExtracts
Build-up of VIT
Patient
MedicalFactors
Logistic
OtherFactors
Financial
Extract
Purified
Non Purified
Depot
Pretreatment
Antihistamines
Omalizumab
Montelukast
Others
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Pretreatment
Extract
Patient
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Rush VIT by Sturm et al (60 min)6
Day 1 Day 2 Day 3 Day 4
0001 08 8 80
001 10 10 100
01 20 20
02 40 40
04 60 60
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
079 Bee012 Vespid
=
Sturm G Kraumlnke B Rudolph C Aberer W Rush Hymenoptera venom immunotherapy a safe and practical protocol for high-risk patients J Allergy Clin Immunol 2002 Dec110(6)928-33
1 High risk of future severe reactions case history and test results
2 High risk for side effects of venom immunotherapy (elderly persons with coexisting internal disease)
3 Need protection soon
4 Rural areas
5 Highly sensitized and anxious
6 Highly sensitized children
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Sturm G Kraumlnke B Rudolph C Aberer W Rush Hymenoptera venom immunotherapy a safe and practical protocol for high-risk patients J Allergy Clin Immunol 2002 Dec110(6)928-33
Day
Venom
concentration
mcgmL
Volume mL Dose mcg
Daily
accumulative
dose mcg
1
1 005 005
1 01 01
1 02 02
1 04 04
1 08 08
10 02 2
10 05 5
10 10 10
100 02 20
100 02 20 5855
2
100 02 20
100 03 30
100 05 50 100
3 100 10 100 100
There were 15-min intervals between venom injections
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Goldberg A Confino-Cohen R Rush venom immunotherapy
in patients experiencing recurrent systemic reactions
to conventional venom immunotherapy Ann Allergy
Asthma Immunol 2003 Oct91(4)405-10
The Bonn Rush VIT protocol (100000 SQ-E=100 mcg insect venom)
Day Preparation Concentration(mcgmL) Volume (mL) Dose (mcg)
1 (Monday) Lyophilisate 0000001 02 00000002
000001 02 0000002
00001 02 000002
0001 02 00002
2 (Tuesday) Lyophilisate 001 02 0002
001 04 0004
001 08 0008
01 02 002
3 (Wednesday)
Lyophilisate 01 04 004
01 08 008
1 02 02
1 04 04
4 (Thursday) Lyophilisate 1 08 08
10 02 02
10 04 04
10 08 08
5 (Friday) Lyophilisate 100 02 20
100 03 30
100 04 40
100 05 50
6 (Monday) Lyophilisate 100 06 60
100 07 70
100 08 80
7 (Tuesday) LyophilisateDepot
100 09 90
100 1 100
Total Dose 55555
Build-up of VIT
Wenzel J Meissner-Kraemer M Bauer R Bieber T Gerdsen R Safety of rush insect venom
immunotherapy The results of a retrospective study in 178 patients Allergy 2003
Nov58(11)1176-9
179 SRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Wenzel J Meissner-Kraemer M Bauer R Bieber T Gerdsen R Safety of rush insect venom
immunotherapy The results of a retrospective study in 178 patients Allergy 2003
Nov58(11)1176-9
179 SRs
210 min Ultra-rush Protocol4
Day Time Injected
venom (mcgr)
1
0 h 01
30 min 1
1 h 10
15 h 20
25 h 30
35 h 40
150 50
30 min 50
45 One injection of 100 mcgr
Monthly One injection of 100 mcgr
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SRs1279
HBV 30gtYJV 32
Birnbaum J Ramadour M Magnan A Vervloet D Hymenoptera ultra-rush venom immunotherapy (210 min) a safety study and risk factors Clin Exp Allergy 2003 Jan33(1)58-64
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brehler R Wolf H Kuumltting B Schnitker J Luger TSafety of a two-day ultrarush insect venom immunotherapy protocol in comparison with protocols of longer duration and involving a larger number of injections J Allergy Clin Immunol
2000 Jun105(6 Pt 1)1231-5
212 adverse
reactions
darrSRharr darr Injections
Day Dose ml administered Mcgr administered Conc mcgml
1
1 010 001 01
2 010 01 1
3 010 1 10
4 020 2 10
2
5 030 3 10
6 035 35 10
7 035 35 10
3
8 010 10 100
9 015 15 100
10 015 15 100
4
11 020 20 100
12 025 25 100
13 025 25 100
5
14 030 30 100
15 035 35 100
16 035 35 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Bilograve MB Cinti B Brianzoni MF Braschi MC Bonifazi M Antonicelli LHoneybee venom immunotherapy a comparative study using purified and nonpurified aqueous extracts in patients with normal Basal serum tryptase concentrations J
Allergy (Cairo) 20122012869243
NPA275
PA25
Day DoseMcg
administeredinterval
1
1 01 30 min
2 1 30 min
3 10 30 min
4 20 30 min
5 30 60 min
6 50 60 min
7 7 100
14 8 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Roll A Hofbauer G Ballmer-Weber BK Schmid-Grendelmeier P Safety of specific immunotherapy using a four-hour ultra-rush induction scheme in bee and wasp allergy J
Investig Allergol Clin Immunol 200616(2)79-85
Injection
numberDose (mcg) Interval (min)
1 01 30
2 1 30
3 10 30
4 20 60
5 30 60
6 50 180
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Koumlhli-Wiesner A Stahlberger L Bieli C Stricker T Lauener R Induction of specific immunotherapy with hymenoptera venoms using ultrarush regimen in children safety and tolerance J Allergy (Cairo) 20122012790910
SR 29
SR 12
Ultrarush initiation
Visit 1
At 30 min intervals 01 mcg 1 mcg 3 mcg 10
mcg 20 mcg 30 mcg then
For those allocated the 50-target no more
doses on day 1
For those allocated the 100 mcg target delay
60 min and give 40 mcg
Visit 2
At 20 min intervals
For those allocated the 50-target 25 mcg + 25
mcg
For those allocated the 100-target 50 mcg + 50
mcg
Visit 3 Maintenance dose 50 mcg or 100 mcg
Semirush initiation
Visit 1At 20 min intervals 00001 mcg 0001 mcg
001 mcg
Visit 2 At 20 min intervals 001 01 mcg 03 mcg
Visit 3 At 30 min interval 03mcg 1mcg 3 mcg
Visit 4 At 30 min interval 3mcg 10 mcg
Visit 5 At 30 min interval 10mcg 20 mcg
Visit 6 At 30 min interval 20 mcg 30 mcg
Visit 7For those allocated the 50 mcg target (30 min
interval) 25 mcg 25 mcg
For those allocated the 100mcg (30 min
interval)30 mcg 40 mcg
Visit 8 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval) 50mcg 50 mcg
Visit 9 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval)70 mcg 30 mcg
Visit 10 Maintenance dose 50 mcg or 100 mcg
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
injections
LLR SR
Group A 199 0
Group B 32 09
Group C 36 056
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Patella V Florio G Giuliano A et al Hymenoptera Venom Immunotherapy Tolerance and Efficacy of an UltrarushProtocol versus a Rush and a Slow Conventional Protocol J Allergy (Cairo)20122012192192
P=027
3 Days Rush VIT
Day 1
1mcgmL
10 mcgmL
100 mcgmL
005 01 02 04 08 mL (005 01 02 04 08
mcg)
02 05 1 mL (2 5 10 mcg)
02 02 mL (20 20 mcg)
Day 2
100 mcgmL 02 03 05 mL (20 30 50 mcg)
Day 3
100 mcgmL 1 mL (100 mcg)
Conventional Regimen
1 mcgmL005 01 02 04 mL (005 01
02 04 mcg)
10 mcgmL005 01 02 04 mL (05 1 2 4
mcg)
100 mcgmL
002 005 007 01 02 04
06 08 1 ml (2 5 7 10 20 40
60 80 100 mcg)
Build-up of VIT
Goldberg A Yogev A Confino-Cohen R Three Days Rush Venom Immunotherapy in Bee Allergy Safe Inexpensive and
Instantaneously Effective Int Arch Allergy Immunol201115690-98
296 SRs
(BeegtV)
208SR
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Day Vial Volume (mL) Dosis (mcg)
1
1 01 01
1 02 02
1 04 04
1 08 08
2 02 2
2
2 04 4
2 08 8
3 01 10
3 02 20
3
3 04 40
3 06 60
3 08 80
3 1 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
48 patients
25 LR
2 patients mild SR
Saacutenchez-Morillas L Reantildeo Martos M Rodriacuteguez Mosquera M Iglesias Cadarso A Domiacutenguez Laacutezaro AR Safety of rushimmunotherapy with Hymenoptera venom Allergol Immunopathol (Madr) 200533(4)224-7 Spanish
Vial 1=1 mcgmLVial 2=10 mcgmL
Vial 3=100 mcgmL
Dose administered
(mcg)Time (min)
01 0
1 30
10 60
20 90
30 120
40 150
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Schiavino D Nucera E Pollastrini E De Pasquale T Buonomo A Bartolozzi F Lombardo C Roncallo C Patriarca G Specific ultrarush desensitization in Hymenoptera venom-allergic patients Ann Allergy Asthma Immunol 2004
Apr92(4)409-13
7 mildSRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Build-up of VIT
Patient
MedicalFactors
Logistic
OtherFactors
Financial
Extract
Purified
Non Purified
Depot
Pretreatment
Antihistamines
Omalizumab
Montelukast
Others
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Pretreatment
Extract
Patient
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Rush VIT by Sturm et al (60 min)6
Day 1 Day 2 Day 3 Day 4
0001 08 8 80
001 10 10 100
01 20 20
02 40 40
04 60 60
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
079 Bee012 Vespid
=
Sturm G Kraumlnke B Rudolph C Aberer W Rush Hymenoptera venom immunotherapy a safe and practical protocol for high-risk patients J Allergy Clin Immunol 2002 Dec110(6)928-33
1 High risk of future severe reactions case history and test results
2 High risk for side effects of venom immunotherapy (elderly persons with coexisting internal disease)
3 Need protection soon
4 Rural areas
5 Highly sensitized and anxious
6 Highly sensitized children
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Sturm G Kraumlnke B Rudolph C Aberer W Rush Hymenoptera venom immunotherapy a safe and practical protocol for high-risk patients J Allergy Clin Immunol 2002 Dec110(6)928-33
Day
Venom
concentration
mcgmL
Volume mL Dose mcg
Daily
accumulative
dose mcg
1
1 005 005
1 01 01
1 02 02
1 04 04
1 08 08
10 02 2
10 05 5
10 10 10
100 02 20
100 02 20 5855
2
100 02 20
100 03 30
100 05 50 100
3 100 10 100 100
There were 15-min intervals between venom injections
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Goldberg A Confino-Cohen R Rush venom immunotherapy
in patients experiencing recurrent systemic reactions
to conventional venom immunotherapy Ann Allergy
Asthma Immunol 2003 Oct91(4)405-10
The Bonn Rush VIT protocol (100000 SQ-E=100 mcg insect venom)
Day Preparation Concentration(mcgmL) Volume (mL) Dose (mcg)
1 (Monday) Lyophilisate 0000001 02 00000002
000001 02 0000002
00001 02 000002
0001 02 00002
2 (Tuesday) Lyophilisate 001 02 0002
001 04 0004
001 08 0008
01 02 002
3 (Wednesday)
Lyophilisate 01 04 004
01 08 008
1 02 02
1 04 04
4 (Thursday) Lyophilisate 1 08 08
10 02 02
10 04 04
10 08 08
5 (Friday) Lyophilisate 100 02 20
100 03 30
100 04 40
100 05 50
6 (Monday) Lyophilisate 100 06 60
100 07 70
100 08 80
7 (Tuesday) LyophilisateDepot
100 09 90
100 1 100
Total Dose 55555
Build-up of VIT
Wenzel J Meissner-Kraemer M Bauer R Bieber T Gerdsen R Safety of rush insect venom
immunotherapy The results of a retrospective study in 178 patients Allergy 2003
Nov58(11)1176-9
179 SRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Wenzel J Meissner-Kraemer M Bauer R Bieber T Gerdsen R Safety of rush insect venom
immunotherapy The results of a retrospective study in 178 patients Allergy 2003
Nov58(11)1176-9
179 SRs
210 min Ultra-rush Protocol4
Day Time Injected
venom (mcgr)
1
0 h 01
30 min 1
1 h 10
15 h 20
25 h 30
35 h 40
150 50
30 min 50
45 One injection of 100 mcgr
Monthly One injection of 100 mcgr
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SRs1279
HBV 30gtYJV 32
Birnbaum J Ramadour M Magnan A Vervloet D Hymenoptera ultra-rush venom immunotherapy (210 min) a safety study and risk factors Clin Exp Allergy 2003 Jan33(1)58-64
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brehler R Wolf H Kuumltting B Schnitker J Luger TSafety of a two-day ultrarush insect venom immunotherapy protocol in comparison with protocols of longer duration and involving a larger number of injections J Allergy Clin Immunol
2000 Jun105(6 Pt 1)1231-5
212 adverse
reactions
darrSRharr darr Injections
Day Dose ml administered Mcgr administered Conc mcgml
1
1 010 001 01
2 010 01 1
3 010 1 10
4 020 2 10
2
5 030 3 10
6 035 35 10
7 035 35 10
3
8 010 10 100
9 015 15 100
10 015 15 100
4
11 020 20 100
12 025 25 100
13 025 25 100
5
14 030 30 100
15 035 35 100
16 035 35 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Bilograve MB Cinti B Brianzoni MF Braschi MC Bonifazi M Antonicelli LHoneybee venom immunotherapy a comparative study using purified and nonpurified aqueous extracts in patients with normal Basal serum tryptase concentrations J
Allergy (Cairo) 20122012869243
NPA275
PA25
Day DoseMcg
administeredinterval
1
1 01 30 min
2 1 30 min
3 10 30 min
4 20 30 min
5 30 60 min
6 50 60 min
7 7 100
14 8 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Roll A Hofbauer G Ballmer-Weber BK Schmid-Grendelmeier P Safety of specific immunotherapy using a four-hour ultra-rush induction scheme in bee and wasp allergy J
Investig Allergol Clin Immunol 200616(2)79-85
Injection
numberDose (mcg) Interval (min)
1 01 30
2 1 30
3 10 30
4 20 60
5 30 60
6 50 180
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Koumlhli-Wiesner A Stahlberger L Bieli C Stricker T Lauener R Induction of specific immunotherapy with hymenoptera venoms using ultrarush regimen in children safety and tolerance J Allergy (Cairo) 20122012790910
SR 29
SR 12
Ultrarush initiation
Visit 1
At 30 min intervals 01 mcg 1 mcg 3 mcg 10
mcg 20 mcg 30 mcg then
For those allocated the 50-target no more
doses on day 1
For those allocated the 100 mcg target delay
60 min and give 40 mcg
Visit 2
At 20 min intervals
For those allocated the 50-target 25 mcg + 25
mcg
For those allocated the 100-target 50 mcg + 50
mcg
Visit 3 Maintenance dose 50 mcg or 100 mcg
Semirush initiation
Visit 1At 20 min intervals 00001 mcg 0001 mcg
001 mcg
Visit 2 At 20 min intervals 001 01 mcg 03 mcg
Visit 3 At 30 min interval 03mcg 1mcg 3 mcg
Visit 4 At 30 min interval 3mcg 10 mcg
Visit 5 At 30 min interval 10mcg 20 mcg
Visit 6 At 30 min interval 20 mcg 30 mcg
Visit 7For those allocated the 50 mcg target (30 min
interval) 25 mcg 25 mcg
For those allocated the 100mcg (30 min
interval)30 mcg 40 mcg
Visit 8 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval) 50mcg 50 mcg
Visit 9 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval)70 mcg 30 mcg
Visit 10 Maintenance dose 50 mcg or 100 mcg
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
injections
LLR SR
Group A 199 0
Group B 32 09
Group C 36 056
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Patella V Florio G Giuliano A et al Hymenoptera Venom Immunotherapy Tolerance and Efficacy of an UltrarushProtocol versus a Rush and a Slow Conventional Protocol J Allergy (Cairo)20122012192192
P=027
3 Days Rush VIT
Day 1
1mcgmL
10 mcgmL
100 mcgmL
005 01 02 04 08 mL (005 01 02 04 08
mcg)
02 05 1 mL (2 5 10 mcg)
02 02 mL (20 20 mcg)
Day 2
100 mcgmL 02 03 05 mL (20 30 50 mcg)
Day 3
100 mcgmL 1 mL (100 mcg)
Conventional Regimen
1 mcgmL005 01 02 04 mL (005 01
02 04 mcg)
10 mcgmL005 01 02 04 mL (05 1 2 4
mcg)
100 mcgmL
002 005 007 01 02 04
06 08 1 ml (2 5 7 10 20 40
60 80 100 mcg)
Build-up of VIT
Goldberg A Yogev A Confino-Cohen R Three Days Rush Venom Immunotherapy in Bee Allergy Safe Inexpensive and
Instantaneously Effective Int Arch Allergy Immunol201115690-98
296 SRs
(BeegtV)
208SR
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Day Vial Volume (mL) Dosis (mcg)
1
1 01 01
1 02 02
1 04 04
1 08 08
2 02 2
2
2 04 4
2 08 8
3 01 10
3 02 20
3
3 04 40
3 06 60
3 08 80
3 1 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
48 patients
25 LR
2 patients mild SR
Saacutenchez-Morillas L Reantildeo Martos M Rodriacuteguez Mosquera M Iglesias Cadarso A Domiacutenguez Laacutezaro AR Safety of rushimmunotherapy with Hymenoptera venom Allergol Immunopathol (Madr) 200533(4)224-7 Spanish
Vial 1=1 mcgmLVial 2=10 mcgmL
Vial 3=100 mcgmL
Dose administered
(mcg)Time (min)
01 0
1 30
10 60
20 90
30 120
40 150
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Schiavino D Nucera E Pollastrini E De Pasquale T Buonomo A Bartolozzi F Lombardo C Roncallo C Patriarca G Specific ultrarush desensitization in Hymenoptera venom-allergic patients Ann Allergy Asthma Immunol 2004
Apr92(4)409-13
7 mildSRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Pretreatment
Extract
Patient
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Rush VIT by Sturm et al (60 min)6
Day 1 Day 2 Day 3 Day 4
0001 08 8 80
001 10 10 100
01 20 20
02 40 40
04 60 60
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
079 Bee012 Vespid
=
Sturm G Kraumlnke B Rudolph C Aberer W Rush Hymenoptera venom immunotherapy a safe and practical protocol for high-risk patients J Allergy Clin Immunol 2002 Dec110(6)928-33
1 High risk of future severe reactions case history and test results
2 High risk for side effects of venom immunotherapy (elderly persons with coexisting internal disease)
3 Need protection soon
4 Rural areas
5 Highly sensitized and anxious
6 Highly sensitized children
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Sturm G Kraumlnke B Rudolph C Aberer W Rush Hymenoptera venom immunotherapy a safe and practical protocol for high-risk patients J Allergy Clin Immunol 2002 Dec110(6)928-33
Day
Venom
concentration
mcgmL
Volume mL Dose mcg
Daily
accumulative
dose mcg
1
1 005 005
1 01 01
1 02 02
1 04 04
1 08 08
10 02 2
10 05 5
10 10 10
100 02 20
100 02 20 5855
2
100 02 20
100 03 30
100 05 50 100
3 100 10 100 100
There were 15-min intervals between venom injections
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Goldberg A Confino-Cohen R Rush venom immunotherapy
in patients experiencing recurrent systemic reactions
to conventional venom immunotherapy Ann Allergy
Asthma Immunol 2003 Oct91(4)405-10
The Bonn Rush VIT protocol (100000 SQ-E=100 mcg insect venom)
Day Preparation Concentration(mcgmL) Volume (mL) Dose (mcg)
1 (Monday) Lyophilisate 0000001 02 00000002
000001 02 0000002
00001 02 000002
0001 02 00002
2 (Tuesday) Lyophilisate 001 02 0002
001 04 0004
001 08 0008
01 02 002
3 (Wednesday)
Lyophilisate 01 04 004
01 08 008
1 02 02
1 04 04
4 (Thursday) Lyophilisate 1 08 08
10 02 02
10 04 04
10 08 08
5 (Friday) Lyophilisate 100 02 20
100 03 30
100 04 40
100 05 50
6 (Monday) Lyophilisate 100 06 60
100 07 70
100 08 80
7 (Tuesday) LyophilisateDepot
100 09 90
100 1 100
Total Dose 55555
Build-up of VIT
Wenzel J Meissner-Kraemer M Bauer R Bieber T Gerdsen R Safety of rush insect venom
immunotherapy The results of a retrospective study in 178 patients Allergy 2003
Nov58(11)1176-9
179 SRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Wenzel J Meissner-Kraemer M Bauer R Bieber T Gerdsen R Safety of rush insect venom
immunotherapy The results of a retrospective study in 178 patients Allergy 2003
Nov58(11)1176-9
179 SRs
210 min Ultra-rush Protocol4
Day Time Injected
venom (mcgr)
1
0 h 01
30 min 1
1 h 10
15 h 20
25 h 30
35 h 40
150 50
30 min 50
45 One injection of 100 mcgr
Monthly One injection of 100 mcgr
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SRs1279
HBV 30gtYJV 32
Birnbaum J Ramadour M Magnan A Vervloet D Hymenoptera ultra-rush venom immunotherapy (210 min) a safety study and risk factors Clin Exp Allergy 2003 Jan33(1)58-64
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brehler R Wolf H Kuumltting B Schnitker J Luger TSafety of a two-day ultrarush insect venom immunotherapy protocol in comparison with protocols of longer duration and involving a larger number of injections J Allergy Clin Immunol
2000 Jun105(6 Pt 1)1231-5
212 adverse
reactions
darrSRharr darr Injections
Day Dose ml administered Mcgr administered Conc mcgml
1
1 010 001 01
2 010 01 1
3 010 1 10
4 020 2 10
2
5 030 3 10
6 035 35 10
7 035 35 10
3
8 010 10 100
9 015 15 100
10 015 15 100
4
11 020 20 100
12 025 25 100
13 025 25 100
5
14 030 30 100
15 035 35 100
16 035 35 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Bilograve MB Cinti B Brianzoni MF Braschi MC Bonifazi M Antonicelli LHoneybee venom immunotherapy a comparative study using purified and nonpurified aqueous extracts in patients with normal Basal serum tryptase concentrations J
Allergy (Cairo) 20122012869243
NPA275
PA25
Day DoseMcg
administeredinterval
1
1 01 30 min
2 1 30 min
3 10 30 min
4 20 30 min
5 30 60 min
6 50 60 min
7 7 100
14 8 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Roll A Hofbauer G Ballmer-Weber BK Schmid-Grendelmeier P Safety of specific immunotherapy using a four-hour ultra-rush induction scheme in bee and wasp allergy J
Investig Allergol Clin Immunol 200616(2)79-85
Injection
numberDose (mcg) Interval (min)
1 01 30
2 1 30
3 10 30
4 20 60
5 30 60
6 50 180
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Koumlhli-Wiesner A Stahlberger L Bieli C Stricker T Lauener R Induction of specific immunotherapy with hymenoptera venoms using ultrarush regimen in children safety and tolerance J Allergy (Cairo) 20122012790910
SR 29
SR 12
Ultrarush initiation
Visit 1
At 30 min intervals 01 mcg 1 mcg 3 mcg 10
mcg 20 mcg 30 mcg then
For those allocated the 50-target no more
doses on day 1
For those allocated the 100 mcg target delay
60 min and give 40 mcg
Visit 2
At 20 min intervals
For those allocated the 50-target 25 mcg + 25
mcg
For those allocated the 100-target 50 mcg + 50
mcg
Visit 3 Maintenance dose 50 mcg or 100 mcg
Semirush initiation
Visit 1At 20 min intervals 00001 mcg 0001 mcg
001 mcg
Visit 2 At 20 min intervals 001 01 mcg 03 mcg
Visit 3 At 30 min interval 03mcg 1mcg 3 mcg
Visit 4 At 30 min interval 3mcg 10 mcg
Visit 5 At 30 min interval 10mcg 20 mcg
Visit 6 At 30 min interval 20 mcg 30 mcg
Visit 7For those allocated the 50 mcg target (30 min
interval) 25 mcg 25 mcg
For those allocated the 100mcg (30 min
interval)30 mcg 40 mcg
Visit 8 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval) 50mcg 50 mcg
Visit 9 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval)70 mcg 30 mcg
Visit 10 Maintenance dose 50 mcg or 100 mcg
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
injections
LLR SR
Group A 199 0
Group B 32 09
Group C 36 056
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Patella V Florio G Giuliano A et al Hymenoptera Venom Immunotherapy Tolerance and Efficacy of an UltrarushProtocol versus a Rush and a Slow Conventional Protocol J Allergy (Cairo)20122012192192
P=027
3 Days Rush VIT
Day 1
1mcgmL
10 mcgmL
100 mcgmL
005 01 02 04 08 mL (005 01 02 04 08
mcg)
02 05 1 mL (2 5 10 mcg)
02 02 mL (20 20 mcg)
Day 2
100 mcgmL 02 03 05 mL (20 30 50 mcg)
Day 3
100 mcgmL 1 mL (100 mcg)
Conventional Regimen
1 mcgmL005 01 02 04 mL (005 01
02 04 mcg)
10 mcgmL005 01 02 04 mL (05 1 2 4
mcg)
100 mcgmL
002 005 007 01 02 04
06 08 1 ml (2 5 7 10 20 40
60 80 100 mcg)
Build-up of VIT
Goldberg A Yogev A Confino-Cohen R Three Days Rush Venom Immunotherapy in Bee Allergy Safe Inexpensive and
Instantaneously Effective Int Arch Allergy Immunol201115690-98
296 SRs
(BeegtV)
208SR
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Day Vial Volume (mL) Dosis (mcg)
1
1 01 01
1 02 02
1 04 04
1 08 08
2 02 2
2
2 04 4
2 08 8
3 01 10
3 02 20
3
3 04 40
3 06 60
3 08 80
3 1 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
48 patients
25 LR
2 patients mild SR
Saacutenchez-Morillas L Reantildeo Martos M Rodriacuteguez Mosquera M Iglesias Cadarso A Domiacutenguez Laacutezaro AR Safety of rushimmunotherapy with Hymenoptera venom Allergol Immunopathol (Madr) 200533(4)224-7 Spanish
Vial 1=1 mcgmLVial 2=10 mcgmL
Vial 3=100 mcgmL
Dose administered
(mcg)Time (min)
01 0
1 30
10 60
20 90
30 120
40 150
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Schiavino D Nucera E Pollastrini E De Pasquale T Buonomo A Bartolozzi F Lombardo C Roncallo C Patriarca G Specific ultrarush desensitization in Hymenoptera venom-allergic patients Ann Allergy Asthma Immunol 2004
Apr92(4)409-13
7 mildSRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Rush VIT by Sturm et al (60 min)6
Day 1 Day 2 Day 3 Day 4
0001 08 8 80
001 10 10 100
01 20 20
02 40 40
04 60 60
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
079 Bee012 Vespid
=
Sturm G Kraumlnke B Rudolph C Aberer W Rush Hymenoptera venom immunotherapy a safe and practical protocol for high-risk patients J Allergy Clin Immunol 2002 Dec110(6)928-33
1 High risk of future severe reactions case history and test results
2 High risk for side effects of venom immunotherapy (elderly persons with coexisting internal disease)
3 Need protection soon
4 Rural areas
5 Highly sensitized and anxious
6 Highly sensitized children
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Sturm G Kraumlnke B Rudolph C Aberer W Rush Hymenoptera venom immunotherapy a safe and practical protocol for high-risk patients J Allergy Clin Immunol 2002 Dec110(6)928-33
Day
Venom
concentration
mcgmL
Volume mL Dose mcg
Daily
accumulative
dose mcg
1
1 005 005
1 01 01
1 02 02
1 04 04
1 08 08
10 02 2
10 05 5
10 10 10
100 02 20
100 02 20 5855
2
100 02 20
100 03 30
100 05 50 100
3 100 10 100 100
There were 15-min intervals between venom injections
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Goldberg A Confino-Cohen R Rush venom immunotherapy
in patients experiencing recurrent systemic reactions
to conventional venom immunotherapy Ann Allergy
Asthma Immunol 2003 Oct91(4)405-10
The Bonn Rush VIT protocol (100000 SQ-E=100 mcg insect venom)
Day Preparation Concentration(mcgmL) Volume (mL) Dose (mcg)
1 (Monday) Lyophilisate 0000001 02 00000002
000001 02 0000002
00001 02 000002
0001 02 00002
2 (Tuesday) Lyophilisate 001 02 0002
001 04 0004
001 08 0008
01 02 002
3 (Wednesday)
Lyophilisate 01 04 004
01 08 008
1 02 02
1 04 04
4 (Thursday) Lyophilisate 1 08 08
10 02 02
10 04 04
10 08 08
5 (Friday) Lyophilisate 100 02 20
100 03 30
100 04 40
100 05 50
6 (Monday) Lyophilisate 100 06 60
100 07 70
100 08 80
7 (Tuesday) LyophilisateDepot
100 09 90
100 1 100
Total Dose 55555
Build-up of VIT
Wenzel J Meissner-Kraemer M Bauer R Bieber T Gerdsen R Safety of rush insect venom
immunotherapy The results of a retrospective study in 178 patients Allergy 2003
Nov58(11)1176-9
179 SRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Wenzel J Meissner-Kraemer M Bauer R Bieber T Gerdsen R Safety of rush insect venom
immunotherapy The results of a retrospective study in 178 patients Allergy 2003
Nov58(11)1176-9
179 SRs
210 min Ultra-rush Protocol4
Day Time Injected
venom (mcgr)
1
0 h 01
30 min 1
1 h 10
15 h 20
25 h 30
35 h 40
150 50
30 min 50
45 One injection of 100 mcgr
Monthly One injection of 100 mcgr
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SRs1279
HBV 30gtYJV 32
Birnbaum J Ramadour M Magnan A Vervloet D Hymenoptera ultra-rush venom immunotherapy (210 min) a safety study and risk factors Clin Exp Allergy 2003 Jan33(1)58-64
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brehler R Wolf H Kuumltting B Schnitker J Luger TSafety of a two-day ultrarush insect venom immunotherapy protocol in comparison with protocols of longer duration and involving a larger number of injections J Allergy Clin Immunol
2000 Jun105(6 Pt 1)1231-5
212 adverse
reactions
darrSRharr darr Injections
Day Dose ml administered Mcgr administered Conc mcgml
1
1 010 001 01
2 010 01 1
3 010 1 10
4 020 2 10
2
5 030 3 10
6 035 35 10
7 035 35 10
3
8 010 10 100
9 015 15 100
10 015 15 100
4
11 020 20 100
12 025 25 100
13 025 25 100
5
14 030 30 100
15 035 35 100
16 035 35 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Bilograve MB Cinti B Brianzoni MF Braschi MC Bonifazi M Antonicelli LHoneybee venom immunotherapy a comparative study using purified and nonpurified aqueous extracts in patients with normal Basal serum tryptase concentrations J
Allergy (Cairo) 20122012869243
NPA275
PA25
Day DoseMcg
administeredinterval
1
1 01 30 min
2 1 30 min
3 10 30 min
4 20 30 min
5 30 60 min
6 50 60 min
7 7 100
14 8 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Roll A Hofbauer G Ballmer-Weber BK Schmid-Grendelmeier P Safety of specific immunotherapy using a four-hour ultra-rush induction scheme in bee and wasp allergy J
Investig Allergol Clin Immunol 200616(2)79-85
Injection
numberDose (mcg) Interval (min)
1 01 30
2 1 30
3 10 30
4 20 60
5 30 60
6 50 180
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Koumlhli-Wiesner A Stahlberger L Bieli C Stricker T Lauener R Induction of specific immunotherapy with hymenoptera venoms using ultrarush regimen in children safety and tolerance J Allergy (Cairo) 20122012790910
SR 29
SR 12
Ultrarush initiation
Visit 1
At 30 min intervals 01 mcg 1 mcg 3 mcg 10
mcg 20 mcg 30 mcg then
For those allocated the 50-target no more
doses on day 1
For those allocated the 100 mcg target delay
60 min and give 40 mcg
Visit 2
At 20 min intervals
For those allocated the 50-target 25 mcg + 25
mcg
For those allocated the 100-target 50 mcg + 50
mcg
Visit 3 Maintenance dose 50 mcg or 100 mcg
Semirush initiation
Visit 1At 20 min intervals 00001 mcg 0001 mcg
001 mcg
Visit 2 At 20 min intervals 001 01 mcg 03 mcg
Visit 3 At 30 min interval 03mcg 1mcg 3 mcg
Visit 4 At 30 min interval 3mcg 10 mcg
Visit 5 At 30 min interval 10mcg 20 mcg
Visit 6 At 30 min interval 20 mcg 30 mcg
Visit 7For those allocated the 50 mcg target (30 min
interval) 25 mcg 25 mcg
For those allocated the 100mcg (30 min
interval)30 mcg 40 mcg
Visit 8 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval) 50mcg 50 mcg
Visit 9 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval)70 mcg 30 mcg
Visit 10 Maintenance dose 50 mcg or 100 mcg
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
injections
LLR SR
Group A 199 0
Group B 32 09
Group C 36 056
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Patella V Florio G Giuliano A et al Hymenoptera Venom Immunotherapy Tolerance and Efficacy of an UltrarushProtocol versus a Rush and a Slow Conventional Protocol J Allergy (Cairo)20122012192192
P=027
3 Days Rush VIT
Day 1
1mcgmL
10 mcgmL
100 mcgmL
005 01 02 04 08 mL (005 01 02 04 08
mcg)
02 05 1 mL (2 5 10 mcg)
02 02 mL (20 20 mcg)
Day 2
100 mcgmL 02 03 05 mL (20 30 50 mcg)
Day 3
100 mcgmL 1 mL (100 mcg)
Conventional Regimen
1 mcgmL005 01 02 04 mL (005 01
02 04 mcg)
10 mcgmL005 01 02 04 mL (05 1 2 4
mcg)
100 mcgmL
002 005 007 01 02 04
06 08 1 ml (2 5 7 10 20 40
60 80 100 mcg)
Build-up of VIT
Goldberg A Yogev A Confino-Cohen R Three Days Rush Venom Immunotherapy in Bee Allergy Safe Inexpensive and
Instantaneously Effective Int Arch Allergy Immunol201115690-98
296 SRs
(BeegtV)
208SR
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Day Vial Volume (mL) Dosis (mcg)
1
1 01 01
1 02 02
1 04 04
1 08 08
2 02 2
2
2 04 4
2 08 8
3 01 10
3 02 20
3
3 04 40
3 06 60
3 08 80
3 1 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
48 patients
25 LR
2 patients mild SR
Saacutenchez-Morillas L Reantildeo Martos M Rodriacuteguez Mosquera M Iglesias Cadarso A Domiacutenguez Laacutezaro AR Safety of rushimmunotherapy with Hymenoptera venom Allergol Immunopathol (Madr) 200533(4)224-7 Spanish
Vial 1=1 mcgmLVial 2=10 mcgmL
Vial 3=100 mcgmL
Dose administered
(mcg)Time (min)
01 0
1 30
10 60
20 90
30 120
40 150
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Schiavino D Nucera E Pollastrini E De Pasquale T Buonomo A Bartolozzi F Lombardo C Roncallo C Patriarca G Specific ultrarush desensitization in Hymenoptera venom-allergic patients Ann Allergy Asthma Immunol 2004
Apr92(4)409-13
7 mildSRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
1 High risk of future severe reactions case history and test results
2 High risk for side effects of venom immunotherapy (elderly persons with coexisting internal disease)
3 Need protection soon
4 Rural areas
5 Highly sensitized and anxious
6 Highly sensitized children
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Sturm G Kraumlnke B Rudolph C Aberer W Rush Hymenoptera venom immunotherapy a safe and practical protocol for high-risk patients J Allergy Clin Immunol 2002 Dec110(6)928-33
Day
Venom
concentration
mcgmL
Volume mL Dose mcg
Daily
accumulative
dose mcg
1
1 005 005
1 01 01
1 02 02
1 04 04
1 08 08
10 02 2
10 05 5
10 10 10
100 02 20
100 02 20 5855
2
100 02 20
100 03 30
100 05 50 100
3 100 10 100 100
There were 15-min intervals between venom injections
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Goldberg A Confino-Cohen R Rush venom immunotherapy
in patients experiencing recurrent systemic reactions
to conventional venom immunotherapy Ann Allergy
Asthma Immunol 2003 Oct91(4)405-10
The Bonn Rush VIT protocol (100000 SQ-E=100 mcg insect venom)
Day Preparation Concentration(mcgmL) Volume (mL) Dose (mcg)
1 (Monday) Lyophilisate 0000001 02 00000002
000001 02 0000002
00001 02 000002
0001 02 00002
2 (Tuesday) Lyophilisate 001 02 0002
001 04 0004
001 08 0008
01 02 002
3 (Wednesday)
Lyophilisate 01 04 004
01 08 008
1 02 02
1 04 04
4 (Thursday) Lyophilisate 1 08 08
10 02 02
10 04 04
10 08 08
5 (Friday) Lyophilisate 100 02 20
100 03 30
100 04 40
100 05 50
6 (Monday) Lyophilisate 100 06 60
100 07 70
100 08 80
7 (Tuesday) LyophilisateDepot
100 09 90
100 1 100
Total Dose 55555
Build-up of VIT
Wenzel J Meissner-Kraemer M Bauer R Bieber T Gerdsen R Safety of rush insect venom
immunotherapy The results of a retrospective study in 178 patients Allergy 2003
Nov58(11)1176-9
179 SRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Wenzel J Meissner-Kraemer M Bauer R Bieber T Gerdsen R Safety of rush insect venom
immunotherapy The results of a retrospective study in 178 patients Allergy 2003
Nov58(11)1176-9
179 SRs
210 min Ultra-rush Protocol4
Day Time Injected
venom (mcgr)
1
0 h 01
30 min 1
1 h 10
15 h 20
25 h 30
35 h 40
150 50
30 min 50
45 One injection of 100 mcgr
Monthly One injection of 100 mcgr
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SRs1279
HBV 30gtYJV 32
Birnbaum J Ramadour M Magnan A Vervloet D Hymenoptera ultra-rush venom immunotherapy (210 min) a safety study and risk factors Clin Exp Allergy 2003 Jan33(1)58-64
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brehler R Wolf H Kuumltting B Schnitker J Luger TSafety of a two-day ultrarush insect venom immunotherapy protocol in comparison with protocols of longer duration and involving a larger number of injections J Allergy Clin Immunol
2000 Jun105(6 Pt 1)1231-5
212 adverse
reactions
darrSRharr darr Injections
Day Dose ml administered Mcgr administered Conc mcgml
1
1 010 001 01
2 010 01 1
3 010 1 10
4 020 2 10
2
5 030 3 10
6 035 35 10
7 035 35 10
3
8 010 10 100
9 015 15 100
10 015 15 100
4
11 020 20 100
12 025 25 100
13 025 25 100
5
14 030 30 100
15 035 35 100
16 035 35 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Bilograve MB Cinti B Brianzoni MF Braschi MC Bonifazi M Antonicelli LHoneybee venom immunotherapy a comparative study using purified and nonpurified aqueous extracts in patients with normal Basal serum tryptase concentrations J
Allergy (Cairo) 20122012869243
NPA275
PA25
Day DoseMcg
administeredinterval
1
1 01 30 min
2 1 30 min
3 10 30 min
4 20 30 min
5 30 60 min
6 50 60 min
7 7 100
14 8 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Roll A Hofbauer G Ballmer-Weber BK Schmid-Grendelmeier P Safety of specific immunotherapy using a four-hour ultra-rush induction scheme in bee and wasp allergy J
Investig Allergol Clin Immunol 200616(2)79-85
Injection
numberDose (mcg) Interval (min)
1 01 30
2 1 30
3 10 30
4 20 60
5 30 60
6 50 180
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Koumlhli-Wiesner A Stahlberger L Bieli C Stricker T Lauener R Induction of specific immunotherapy with hymenoptera venoms using ultrarush regimen in children safety and tolerance J Allergy (Cairo) 20122012790910
SR 29
SR 12
Ultrarush initiation
Visit 1
At 30 min intervals 01 mcg 1 mcg 3 mcg 10
mcg 20 mcg 30 mcg then
For those allocated the 50-target no more
doses on day 1
For those allocated the 100 mcg target delay
60 min and give 40 mcg
Visit 2
At 20 min intervals
For those allocated the 50-target 25 mcg + 25
mcg
For those allocated the 100-target 50 mcg + 50
mcg
Visit 3 Maintenance dose 50 mcg or 100 mcg
Semirush initiation
Visit 1At 20 min intervals 00001 mcg 0001 mcg
001 mcg
Visit 2 At 20 min intervals 001 01 mcg 03 mcg
Visit 3 At 30 min interval 03mcg 1mcg 3 mcg
Visit 4 At 30 min interval 3mcg 10 mcg
Visit 5 At 30 min interval 10mcg 20 mcg
Visit 6 At 30 min interval 20 mcg 30 mcg
Visit 7For those allocated the 50 mcg target (30 min
interval) 25 mcg 25 mcg
For those allocated the 100mcg (30 min
interval)30 mcg 40 mcg
Visit 8 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval) 50mcg 50 mcg
Visit 9 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval)70 mcg 30 mcg
Visit 10 Maintenance dose 50 mcg or 100 mcg
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
injections
LLR SR
Group A 199 0
Group B 32 09
Group C 36 056
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Patella V Florio G Giuliano A et al Hymenoptera Venom Immunotherapy Tolerance and Efficacy of an UltrarushProtocol versus a Rush and a Slow Conventional Protocol J Allergy (Cairo)20122012192192
P=027
3 Days Rush VIT
Day 1
1mcgmL
10 mcgmL
100 mcgmL
005 01 02 04 08 mL (005 01 02 04 08
mcg)
02 05 1 mL (2 5 10 mcg)
02 02 mL (20 20 mcg)
Day 2
100 mcgmL 02 03 05 mL (20 30 50 mcg)
Day 3
100 mcgmL 1 mL (100 mcg)
Conventional Regimen
1 mcgmL005 01 02 04 mL (005 01
02 04 mcg)
10 mcgmL005 01 02 04 mL (05 1 2 4
mcg)
100 mcgmL
002 005 007 01 02 04
06 08 1 ml (2 5 7 10 20 40
60 80 100 mcg)
Build-up of VIT
Goldberg A Yogev A Confino-Cohen R Three Days Rush Venom Immunotherapy in Bee Allergy Safe Inexpensive and
Instantaneously Effective Int Arch Allergy Immunol201115690-98
296 SRs
(BeegtV)
208SR
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Day Vial Volume (mL) Dosis (mcg)
1
1 01 01
1 02 02
1 04 04
1 08 08
2 02 2
2
2 04 4
2 08 8
3 01 10
3 02 20
3
3 04 40
3 06 60
3 08 80
3 1 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
48 patients
25 LR
2 patients mild SR
Saacutenchez-Morillas L Reantildeo Martos M Rodriacuteguez Mosquera M Iglesias Cadarso A Domiacutenguez Laacutezaro AR Safety of rushimmunotherapy with Hymenoptera venom Allergol Immunopathol (Madr) 200533(4)224-7 Spanish
Vial 1=1 mcgmLVial 2=10 mcgmL
Vial 3=100 mcgmL
Dose administered
(mcg)Time (min)
01 0
1 30
10 60
20 90
30 120
40 150
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Schiavino D Nucera E Pollastrini E De Pasquale T Buonomo A Bartolozzi F Lombardo C Roncallo C Patriarca G Specific ultrarush desensitization in Hymenoptera venom-allergic patients Ann Allergy Asthma Immunol 2004
Apr92(4)409-13
7 mildSRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Day
Venom
concentration
mcgmL
Volume mL Dose mcg
Daily
accumulative
dose mcg
1
1 005 005
1 01 01
1 02 02
1 04 04
1 08 08
10 02 2
10 05 5
10 10 10
100 02 20
100 02 20 5855
2
100 02 20
100 03 30
100 05 50 100
3 100 10 100 100
There were 15-min intervals between venom injections
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Goldberg A Confino-Cohen R Rush venom immunotherapy
in patients experiencing recurrent systemic reactions
to conventional venom immunotherapy Ann Allergy
Asthma Immunol 2003 Oct91(4)405-10
The Bonn Rush VIT protocol (100000 SQ-E=100 mcg insect venom)
Day Preparation Concentration(mcgmL) Volume (mL) Dose (mcg)
1 (Monday) Lyophilisate 0000001 02 00000002
000001 02 0000002
00001 02 000002
0001 02 00002
2 (Tuesday) Lyophilisate 001 02 0002
001 04 0004
001 08 0008
01 02 002
3 (Wednesday)
Lyophilisate 01 04 004
01 08 008
1 02 02
1 04 04
4 (Thursday) Lyophilisate 1 08 08
10 02 02
10 04 04
10 08 08
5 (Friday) Lyophilisate 100 02 20
100 03 30
100 04 40
100 05 50
6 (Monday) Lyophilisate 100 06 60
100 07 70
100 08 80
7 (Tuesday) LyophilisateDepot
100 09 90
100 1 100
Total Dose 55555
Build-up of VIT
Wenzel J Meissner-Kraemer M Bauer R Bieber T Gerdsen R Safety of rush insect venom
immunotherapy The results of a retrospective study in 178 patients Allergy 2003
Nov58(11)1176-9
179 SRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Wenzel J Meissner-Kraemer M Bauer R Bieber T Gerdsen R Safety of rush insect venom
immunotherapy The results of a retrospective study in 178 patients Allergy 2003
Nov58(11)1176-9
179 SRs
210 min Ultra-rush Protocol4
Day Time Injected
venom (mcgr)
1
0 h 01
30 min 1
1 h 10
15 h 20
25 h 30
35 h 40
150 50
30 min 50
45 One injection of 100 mcgr
Monthly One injection of 100 mcgr
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SRs1279
HBV 30gtYJV 32
Birnbaum J Ramadour M Magnan A Vervloet D Hymenoptera ultra-rush venom immunotherapy (210 min) a safety study and risk factors Clin Exp Allergy 2003 Jan33(1)58-64
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brehler R Wolf H Kuumltting B Schnitker J Luger TSafety of a two-day ultrarush insect venom immunotherapy protocol in comparison with protocols of longer duration and involving a larger number of injections J Allergy Clin Immunol
2000 Jun105(6 Pt 1)1231-5
212 adverse
reactions
darrSRharr darr Injections
Day Dose ml administered Mcgr administered Conc mcgml
1
1 010 001 01
2 010 01 1
3 010 1 10
4 020 2 10
2
5 030 3 10
6 035 35 10
7 035 35 10
3
8 010 10 100
9 015 15 100
10 015 15 100
4
11 020 20 100
12 025 25 100
13 025 25 100
5
14 030 30 100
15 035 35 100
16 035 35 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Bilograve MB Cinti B Brianzoni MF Braschi MC Bonifazi M Antonicelli LHoneybee venom immunotherapy a comparative study using purified and nonpurified aqueous extracts in patients with normal Basal serum tryptase concentrations J
Allergy (Cairo) 20122012869243
NPA275
PA25
Day DoseMcg
administeredinterval
1
1 01 30 min
2 1 30 min
3 10 30 min
4 20 30 min
5 30 60 min
6 50 60 min
7 7 100
14 8 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Roll A Hofbauer G Ballmer-Weber BK Schmid-Grendelmeier P Safety of specific immunotherapy using a four-hour ultra-rush induction scheme in bee and wasp allergy J
Investig Allergol Clin Immunol 200616(2)79-85
Injection
numberDose (mcg) Interval (min)
1 01 30
2 1 30
3 10 30
4 20 60
5 30 60
6 50 180
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Koumlhli-Wiesner A Stahlberger L Bieli C Stricker T Lauener R Induction of specific immunotherapy with hymenoptera venoms using ultrarush regimen in children safety and tolerance J Allergy (Cairo) 20122012790910
SR 29
SR 12
Ultrarush initiation
Visit 1
At 30 min intervals 01 mcg 1 mcg 3 mcg 10
mcg 20 mcg 30 mcg then
For those allocated the 50-target no more
doses on day 1
For those allocated the 100 mcg target delay
60 min and give 40 mcg
Visit 2
At 20 min intervals
For those allocated the 50-target 25 mcg + 25
mcg
For those allocated the 100-target 50 mcg + 50
mcg
Visit 3 Maintenance dose 50 mcg or 100 mcg
Semirush initiation
Visit 1At 20 min intervals 00001 mcg 0001 mcg
001 mcg
Visit 2 At 20 min intervals 001 01 mcg 03 mcg
Visit 3 At 30 min interval 03mcg 1mcg 3 mcg
Visit 4 At 30 min interval 3mcg 10 mcg
Visit 5 At 30 min interval 10mcg 20 mcg
Visit 6 At 30 min interval 20 mcg 30 mcg
Visit 7For those allocated the 50 mcg target (30 min
interval) 25 mcg 25 mcg
For those allocated the 100mcg (30 min
interval)30 mcg 40 mcg
Visit 8 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval) 50mcg 50 mcg
Visit 9 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval)70 mcg 30 mcg
Visit 10 Maintenance dose 50 mcg or 100 mcg
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
injections
LLR SR
Group A 199 0
Group B 32 09
Group C 36 056
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Patella V Florio G Giuliano A et al Hymenoptera Venom Immunotherapy Tolerance and Efficacy of an UltrarushProtocol versus a Rush and a Slow Conventional Protocol J Allergy (Cairo)20122012192192
P=027
3 Days Rush VIT
Day 1
1mcgmL
10 mcgmL
100 mcgmL
005 01 02 04 08 mL (005 01 02 04 08
mcg)
02 05 1 mL (2 5 10 mcg)
02 02 mL (20 20 mcg)
Day 2
100 mcgmL 02 03 05 mL (20 30 50 mcg)
Day 3
100 mcgmL 1 mL (100 mcg)
Conventional Regimen
1 mcgmL005 01 02 04 mL (005 01
02 04 mcg)
10 mcgmL005 01 02 04 mL (05 1 2 4
mcg)
100 mcgmL
002 005 007 01 02 04
06 08 1 ml (2 5 7 10 20 40
60 80 100 mcg)
Build-up of VIT
Goldberg A Yogev A Confino-Cohen R Three Days Rush Venom Immunotherapy in Bee Allergy Safe Inexpensive and
Instantaneously Effective Int Arch Allergy Immunol201115690-98
296 SRs
(BeegtV)
208SR
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Day Vial Volume (mL) Dosis (mcg)
1
1 01 01
1 02 02
1 04 04
1 08 08
2 02 2
2
2 04 4
2 08 8
3 01 10
3 02 20
3
3 04 40
3 06 60
3 08 80
3 1 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
48 patients
25 LR
2 patients mild SR
Saacutenchez-Morillas L Reantildeo Martos M Rodriacuteguez Mosquera M Iglesias Cadarso A Domiacutenguez Laacutezaro AR Safety of rushimmunotherapy with Hymenoptera venom Allergol Immunopathol (Madr) 200533(4)224-7 Spanish
Vial 1=1 mcgmLVial 2=10 mcgmL
Vial 3=100 mcgmL
Dose administered
(mcg)Time (min)
01 0
1 30
10 60
20 90
30 120
40 150
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Schiavino D Nucera E Pollastrini E De Pasquale T Buonomo A Bartolozzi F Lombardo C Roncallo C Patriarca G Specific ultrarush desensitization in Hymenoptera venom-allergic patients Ann Allergy Asthma Immunol 2004
Apr92(4)409-13
7 mildSRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
The Bonn Rush VIT protocol (100000 SQ-E=100 mcg insect venom)
Day Preparation Concentration(mcgmL) Volume (mL) Dose (mcg)
1 (Monday) Lyophilisate 0000001 02 00000002
000001 02 0000002
00001 02 000002
0001 02 00002
2 (Tuesday) Lyophilisate 001 02 0002
001 04 0004
001 08 0008
01 02 002
3 (Wednesday)
Lyophilisate 01 04 004
01 08 008
1 02 02
1 04 04
4 (Thursday) Lyophilisate 1 08 08
10 02 02
10 04 04
10 08 08
5 (Friday) Lyophilisate 100 02 20
100 03 30
100 04 40
100 05 50
6 (Monday) Lyophilisate 100 06 60
100 07 70
100 08 80
7 (Tuesday) LyophilisateDepot
100 09 90
100 1 100
Total Dose 55555
Build-up of VIT
Wenzel J Meissner-Kraemer M Bauer R Bieber T Gerdsen R Safety of rush insect venom
immunotherapy The results of a retrospective study in 178 patients Allergy 2003
Nov58(11)1176-9
179 SRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Wenzel J Meissner-Kraemer M Bauer R Bieber T Gerdsen R Safety of rush insect venom
immunotherapy The results of a retrospective study in 178 patients Allergy 2003
Nov58(11)1176-9
179 SRs
210 min Ultra-rush Protocol4
Day Time Injected
venom (mcgr)
1
0 h 01
30 min 1
1 h 10
15 h 20
25 h 30
35 h 40
150 50
30 min 50
45 One injection of 100 mcgr
Monthly One injection of 100 mcgr
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SRs1279
HBV 30gtYJV 32
Birnbaum J Ramadour M Magnan A Vervloet D Hymenoptera ultra-rush venom immunotherapy (210 min) a safety study and risk factors Clin Exp Allergy 2003 Jan33(1)58-64
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brehler R Wolf H Kuumltting B Schnitker J Luger TSafety of a two-day ultrarush insect venom immunotherapy protocol in comparison with protocols of longer duration and involving a larger number of injections J Allergy Clin Immunol
2000 Jun105(6 Pt 1)1231-5
212 adverse
reactions
darrSRharr darr Injections
Day Dose ml administered Mcgr administered Conc mcgml
1
1 010 001 01
2 010 01 1
3 010 1 10
4 020 2 10
2
5 030 3 10
6 035 35 10
7 035 35 10
3
8 010 10 100
9 015 15 100
10 015 15 100
4
11 020 20 100
12 025 25 100
13 025 25 100
5
14 030 30 100
15 035 35 100
16 035 35 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Bilograve MB Cinti B Brianzoni MF Braschi MC Bonifazi M Antonicelli LHoneybee venom immunotherapy a comparative study using purified and nonpurified aqueous extracts in patients with normal Basal serum tryptase concentrations J
Allergy (Cairo) 20122012869243
NPA275
PA25
Day DoseMcg
administeredinterval
1
1 01 30 min
2 1 30 min
3 10 30 min
4 20 30 min
5 30 60 min
6 50 60 min
7 7 100
14 8 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Roll A Hofbauer G Ballmer-Weber BK Schmid-Grendelmeier P Safety of specific immunotherapy using a four-hour ultra-rush induction scheme in bee and wasp allergy J
Investig Allergol Clin Immunol 200616(2)79-85
Injection
numberDose (mcg) Interval (min)
1 01 30
2 1 30
3 10 30
4 20 60
5 30 60
6 50 180
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Koumlhli-Wiesner A Stahlberger L Bieli C Stricker T Lauener R Induction of specific immunotherapy with hymenoptera venoms using ultrarush regimen in children safety and tolerance J Allergy (Cairo) 20122012790910
SR 29
SR 12
Ultrarush initiation
Visit 1
At 30 min intervals 01 mcg 1 mcg 3 mcg 10
mcg 20 mcg 30 mcg then
For those allocated the 50-target no more
doses on day 1
For those allocated the 100 mcg target delay
60 min and give 40 mcg
Visit 2
At 20 min intervals
For those allocated the 50-target 25 mcg + 25
mcg
For those allocated the 100-target 50 mcg + 50
mcg
Visit 3 Maintenance dose 50 mcg or 100 mcg
Semirush initiation
Visit 1At 20 min intervals 00001 mcg 0001 mcg
001 mcg
Visit 2 At 20 min intervals 001 01 mcg 03 mcg
Visit 3 At 30 min interval 03mcg 1mcg 3 mcg
Visit 4 At 30 min interval 3mcg 10 mcg
Visit 5 At 30 min interval 10mcg 20 mcg
Visit 6 At 30 min interval 20 mcg 30 mcg
Visit 7For those allocated the 50 mcg target (30 min
interval) 25 mcg 25 mcg
For those allocated the 100mcg (30 min
interval)30 mcg 40 mcg
Visit 8 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval) 50mcg 50 mcg
Visit 9 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval)70 mcg 30 mcg
Visit 10 Maintenance dose 50 mcg or 100 mcg
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
injections
LLR SR
Group A 199 0
Group B 32 09
Group C 36 056
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Patella V Florio G Giuliano A et al Hymenoptera Venom Immunotherapy Tolerance and Efficacy of an UltrarushProtocol versus a Rush and a Slow Conventional Protocol J Allergy (Cairo)20122012192192
P=027
3 Days Rush VIT
Day 1
1mcgmL
10 mcgmL
100 mcgmL
005 01 02 04 08 mL (005 01 02 04 08
mcg)
02 05 1 mL (2 5 10 mcg)
02 02 mL (20 20 mcg)
Day 2
100 mcgmL 02 03 05 mL (20 30 50 mcg)
Day 3
100 mcgmL 1 mL (100 mcg)
Conventional Regimen
1 mcgmL005 01 02 04 mL (005 01
02 04 mcg)
10 mcgmL005 01 02 04 mL (05 1 2 4
mcg)
100 mcgmL
002 005 007 01 02 04
06 08 1 ml (2 5 7 10 20 40
60 80 100 mcg)
Build-up of VIT
Goldberg A Yogev A Confino-Cohen R Three Days Rush Venom Immunotherapy in Bee Allergy Safe Inexpensive and
Instantaneously Effective Int Arch Allergy Immunol201115690-98
296 SRs
(BeegtV)
208SR
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Day Vial Volume (mL) Dosis (mcg)
1
1 01 01
1 02 02
1 04 04
1 08 08
2 02 2
2
2 04 4
2 08 8
3 01 10
3 02 20
3
3 04 40
3 06 60
3 08 80
3 1 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
48 patients
25 LR
2 patients mild SR
Saacutenchez-Morillas L Reantildeo Martos M Rodriacuteguez Mosquera M Iglesias Cadarso A Domiacutenguez Laacutezaro AR Safety of rushimmunotherapy with Hymenoptera venom Allergol Immunopathol (Madr) 200533(4)224-7 Spanish
Vial 1=1 mcgmLVial 2=10 mcgmL
Vial 3=100 mcgmL
Dose administered
(mcg)Time (min)
01 0
1 30
10 60
20 90
30 120
40 150
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Schiavino D Nucera E Pollastrini E De Pasquale T Buonomo A Bartolozzi F Lombardo C Roncallo C Patriarca G Specific ultrarush desensitization in Hymenoptera venom-allergic patients Ann Allergy Asthma Immunol 2004
Apr92(4)409-13
7 mildSRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Wenzel J Meissner-Kraemer M Bauer R Bieber T Gerdsen R Safety of rush insect venom
immunotherapy The results of a retrospective study in 178 patients Allergy 2003
Nov58(11)1176-9
179 SRs
210 min Ultra-rush Protocol4
Day Time Injected
venom (mcgr)
1
0 h 01
30 min 1
1 h 10
15 h 20
25 h 30
35 h 40
150 50
30 min 50
45 One injection of 100 mcgr
Monthly One injection of 100 mcgr
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SRs1279
HBV 30gtYJV 32
Birnbaum J Ramadour M Magnan A Vervloet D Hymenoptera ultra-rush venom immunotherapy (210 min) a safety study and risk factors Clin Exp Allergy 2003 Jan33(1)58-64
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brehler R Wolf H Kuumltting B Schnitker J Luger TSafety of a two-day ultrarush insect venom immunotherapy protocol in comparison with protocols of longer duration and involving a larger number of injections J Allergy Clin Immunol
2000 Jun105(6 Pt 1)1231-5
212 adverse
reactions
darrSRharr darr Injections
Day Dose ml administered Mcgr administered Conc mcgml
1
1 010 001 01
2 010 01 1
3 010 1 10
4 020 2 10
2
5 030 3 10
6 035 35 10
7 035 35 10
3
8 010 10 100
9 015 15 100
10 015 15 100
4
11 020 20 100
12 025 25 100
13 025 25 100
5
14 030 30 100
15 035 35 100
16 035 35 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Bilograve MB Cinti B Brianzoni MF Braschi MC Bonifazi M Antonicelli LHoneybee venom immunotherapy a comparative study using purified and nonpurified aqueous extracts in patients with normal Basal serum tryptase concentrations J
Allergy (Cairo) 20122012869243
NPA275
PA25
Day DoseMcg
administeredinterval
1
1 01 30 min
2 1 30 min
3 10 30 min
4 20 30 min
5 30 60 min
6 50 60 min
7 7 100
14 8 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Roll A Hofbauer G Ballmer-Weber BK Schmid-Grendelmeier P Safety of specific immunotherapy using a four-hour ultra-rush induction scheme in bee and wasp allergy J
Investig Allergol Clin Immunol 200616(2)79-85
Injection
numberDose (mcg) Interval (min)
1 01 30
2 1 30
3 10 30
4 20 60
5 30 60
6 50 180
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Koumlhli-Wiesner A Stahlberger L Bieli C Stricker T Lauener R Induction of specific immunotherapy with hymenoptera venoms using ultrarush regimen in children safety and tolerance J Allergy (Cairo) 20122012790910
SR 29
SR 12
Ultrarush initiation
Visit 1
At 30 min intervals 01 mcg 1 mcg 3 mcg 10
mcg 20 mcg 30 mcg then
For those allocated the 50-target no more
doses on day 1
For those allocated the 100 mcg target delay
60 min and give 40 mcg
Visit 2
At 20 min intervals
For those allocated the 50-target 25 mcg + 25
mcg
For those allocated the 100-target 50 mcg + 50
mcg
Visit 3 Maintenance dose 50 mcg or 100 mcg
Semirush initiation
Visit 1At 20 min intervals 00001 mcg 0001 mcg
001 mcg
Visit 2 At 20 min intervals 001 01 mcg 03 mcg
Visit 3 At 30 min interval 03mcg 1mcg 3 mcg
Visit 4 At 30 min interval 3mcg 10 mcg
Visit 5 At 30 min interval 10mcg 20 mcg
Visit 6 At 30 min interval 20 mcg 30 mcg
Visit 7For those allocated the 50 mcg target (30 min
interval) 25 mcg 25 mcg
For those allocated the 100mcg (30 min
interval)30 mcg 40 mcg
Visit 8 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval) 50mcg 50 mcg
Visit 9 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval)70 mcg 30 mcg
Visit 10 Maintenance dose 50 mcg or 100 mcg
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
injections
LLR SR
Group A 199 0
Group B 32 09
Group C 36 056
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Patella V Florio G Giuliano A et al Hymenoptera Venom Immunotherapy Tolerance and Efficacy of an UltrarushProtocol versus a Rush and a Slow Conventional Protocol J Allergy (Cairo)20122012192192
P=027
3 Days Rush VIT
Day 1
1mcgmL
10 mcgmL
100 mcgmL
005 01 02 04 08 mL (005 01 02 04 08
mcg)
02 05 1 mL (2 5 10 mcg)
02 02 mL (20 20 mcg)
Day 2
100 mcgmL 02 03 05 mL (20 30 50 mcg)
Day 3
100 mcgmL 1 mL (100 mcg)
Conventional Regimen
1 mcgmL005 01 02 04 mL (005 01
02 04 mcg)
10 mcgmL005 01 02 04 mL (05 1 2 4
mcg)
100 mcgmL
002 005 007 01 02 04
06 08 1 ml (2 5 7 10 20 40
60 80 100 mcg)
Build-up of VIT
Goldberg A Yogev A Confino-Cohen R Three Days Rush Venom Immunotherapy in Bee Allergy Safe Inexpensive and
Instantaneously Effective Int Arch Allergy Immunol201115690-98
296 SRs
(BeegtV)
208SR
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Day Vial Volume (mL) Dosis (mcg)
1
1 01 01
1 02 02
1 04 04
1 08 08
2 02 2
2
2 04 4
2 08 8
3 01 10
3 02 20
3
3 04 40
3 06 60
3 08 80
3 1 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
48 patients
25 LR
2 patients mild SR
Saacutenchez-Morillas L Reantildeo Martos M Rodriacuteguez Mosquera M Iglesias Cadarso A Domiacutenguez Laacutezaro AR Safety of rushimmunotherapy with Hymenoptera venom Allergol Immunopathol (Madr) 200533(4)224-7 Spanish
Vial 1=1 mcgmLVial 2=10 mcgmL
Vial 3=100 mcgmL
Dose administered
(mcg)Time (min)
01 0
1 30
10 60
20 90
30 120
40 150
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Schiavino D Nucera E Pollastrini E De Pasquale T Buonomo A Bartolozzi F Lombardo C Roncallo C Patriarca G Specific ultrarush desensitization in Hymenoptera venom-allergic patients Ann Allergy Asthma Immunol 2004
Apr92(4)409-13
7 mildSRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
210 min Ultra-rush Protocol4
Day Time Injected
venom (mcgr)
1
0 h 01
30 min 1
1 h 10
15 h 20
25 h 30
35 h 40
150 50
30 min 50
45 One injection of 100 mcgr
Monthly One injection of 100 mcgr
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SRs1279
HBV 30gtYJV 32
Birnbaum J Ramadour M Magnan A Vervloet D Hymenoptera ultra-rush venom immunotherapy (210 min) a safety study and risk factors Clin Exp Allergy 2003 Jan33(1)58-64
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brehler R Wolf H Kuumltting B Schnitker J Luger TSafety of a two-day ultrarush insect venom immunotherapy protocol in comparison with protocols of longer duration and involving a larger number of injections J Allergy Clin Immunol
2000 Jun105(6 Pt 1)1231-5
212 adverse
reactions
darrSRharr darr Injections
Day Dose ml administered Mcgr administered Conc mcgml
1
1 010 001 01
2 010 01 1
3 010 1 10
4 020 2 10
2
5 030 3 10
6 035 35 10
7 035 35 10
3
8 010 10 100
9 015 15 100
10 015 15 100
4
11 020 20 100
12 025 25 100
13 025 25 100
5
14 030 30 100
15 035 35 100
16 035 35 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Bilograve MB Cinti B Brianzoni MF Braschi MC Bonifazi M Antonicelli LHoneybee venom immunotherapy a comparative study using purified and nonpurified aqueous extracts in patients with normal Basal serum tryptase concentrations J
Allergy (Cairo) 20122012869243
NPA275
PA25
Day DoseMcg
administeredinterval
1
1 01 30 min
2 1 30 min
3 10 30 min
4 20 30 min
5 30 60 min
6 50 60 min
7 7 100
14 8 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Roll A Hofbauer G Ballmer-Weber BK Schmid-Grendelmeier P Safety of specific immunotherapy using a four-hour ultra-rush induction scheme in bee and wasp allergy J
Investig Allergol Clin Immunol 200616(2)79-85
Injection
numberDose (mcg) Interval (min)
1 01 30
2 1 30
3 10 30
4 20 60
5 30 60
6 50 180
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Koumlhli-Wiesner A Stahlberger L Bieli C Stricker T Lauener R Induction of specific immunotherapy with hymenoptera venoms using ultrarush regimen in children safety and tolerance J Allergy (Cairo) 20122012790910
SR 29
SR 12
Ultrarush initiation
Visit 1
At 30 min intervals 01 mcg 1 mcg 3 mcg 10
mcg 20 mcg 30 mcg then
For those allocated the 50-target no more
doses on day 1
For those allocated the 100 mcg target delay
60 min and give 40 mcg
Visit 2
At 20 min intervals
For those allocated the 50-target 25 mcg + 25
mcg
For those allocated the 100-target 50 mcg + 50
mcg
Visit 3 Maintenance dose 50 mcg or 100 mcg
Semirush initiation
Visit 1At 20 min intervals 00001 mcg 0001 mcg
001 mcg
Visit 2 At 20 min intervals 001 01 mcg 03 mcg
Visit 3 At 30 min interval 03mcg 1mcg 3 mcg
Visit 4 At 30 min interval 3mcg 10 mcg
Visit 5 At 30 min interval 10mcg 20 mcg
Visit 6 At 30 min interval 20 mcg 30 mcg
Visit 7For those allocated the 50 mcg target (30 min
interval) 25 mcg 25 mcg
For those allocated the 100mcg (30 min
interval)30 mcg 40 mcg
Visit 8 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval) 50mcg 50 mcg
Visit 9 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval)70 mcg 30 mcg
Visit 10 Maintenance dose 50 mcg or 100 mcg
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
injections
LLR SR
Group A 199 0
Group B 32 09
Group C 36 056
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Patella V Florio G Giuliano A et al Hymenoptera Venom Immunotherapy Tolerance and Efficacy of an UltrarushProtocol versus a Rush and a Slow Conventional Protocol J Allergy (Cairo)20122012192192
P=027
3 Days Rush VIT
Day 1
1mcgmL
10 mcgmL
100 mcgmL
005 01 02 04 08 mL (005 01 02 04 08
mcg)
02 05 1 mL (2 5 10 mcg)
02 02 mL (20 20 mcg)
Day 2
100 mcgmL 02 03 05 mL (20 30 50 mcg)
Day 3
100 mcgmL 1 mL (100 mcg)
Conventional Regimen
1 mcgmL005 01 02 04 mL (005 01
02 04 mcg)
10 mcgmL005 01 02 04 mL (05 1 2 4
mcg)
100 mcgmL
002 005 007 01 02 04
06 08 1 ml (2 5 7 10 20 40
60 80 100 mcg)
Build-up of VIT
Goldberg A Yogev A Confino-Cohen R Three Days Rush Venom Immunotherapy in Bee Allergy Safe Inexpensive and
Instantaneously Effective Int Arch Allergy Immunol201115690-98
296 SRs
(BeegtV)
208SR
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Day Vial Volume (mL) Dosis (mcg)
1
1 01 01
1 02 02
1 04 04
1 08 08
2 02 2
2
2 04 4
2 08 8
3 01 10
3 02 20
3
3 04 40
3 06 60
3 08 80
3 1 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
48 patients
25 LR
2 patients mild SR
Saacutenchez-Morillas L Reantildeo Martos M Rodriacuteguez Mosquera M Iglesias Cadarso A Domiacutenguez Laacutezaro AR Safety of rushimmunotherapy with Hymenoptera venom Allergol Immunopathol (Madr) 200533(4)224-7 Spanish
Vial 1=1 mcgmLVial 2=10 mcgmL
Vial 3=100 mcgmL
Dose administered
(mcg)Time (min)
01 0
1 30
10 60
20 90
30 120
40 150
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Schiavino D Nucera E Pollastrini E De Pasquale T Buonomo A Bartolozzi F Lombardo C Roncallo C Patriarca G Specific ultrarush desensitization in Hymenoptera venom-allergic patients Ann Allergy Asthma Immunol 2004
Apr92(4)409-13
7 mildSRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brehler R Wolf H Kuumltting B Schnitker J Luger TSafety of a two-day ultrarush insect venom immunotherapy protocol in comparison with protocols of longer duration and involving a larger number of injections J Allergy Clin Immunol
2000 Jun105(6 Pt 1)1231-5
212 adverse
reactions
darrSRharr darr Injections
Day Dose ml administered Mcgr administered Conc mcgml
1
1 010 001 01
2 010 01 1
3 010 1 10
4 020 2 10
2
5 030 3 10
6 035 35 10
7 035 35 10
3
8 010 10 100
9 015 15 100
10 015 15 100
4
11 020 20 100
12 025 25 100
13 025 25 100
5
14 030 30 100
15 035 35 100
16 035 35 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Bilograve MB Cinti B Brianzoni MF Braschi MC Bonifazi M Antonicelli LHoneybee venom immunotherapy a comparative study using purified and nonpurified aqueous extracts in patients with normal Basal serum tryptase concentrations J
Allergy (Cairo) 20122012869243
NPA275
PA25
Day DoseMcg
administeredinterval
1
1 01 30 min
2 1 30 min
3 10 30 min
4 20 30 min
5 30 60 min
6 50 60 min
7 7 100
14 8 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Roll A Hofbauer G Ballmer-Weber BK Schmid-Grendelmeier P Safety of specific immunotherapy using a four-hour ultra-rush induction scheme in bee and wasp allergy J
Investig Allergol Clin Immunol 200616(2)79-85
Injection
numberDose (mcg) Interval (min)
1 01 30
2 1 30
3 10 30
4 20 60
5 30 60
6 50 180
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Koumlhli-Wiesner A Stahlberger L Bieli C Stricker T Lauener R Induction of specific immunotherapy with hymenoptera venoms using ultrarush regimen in children safety and tolerance J Allergy (Cairo) 20122012790910
SR 29
SR 12
Ultrarush initiation
Visit 1
At 30 min intervals 01 mcg 1 mcg 3 mcg 10
mcg 20 mcg 30 mcg then
For those allocated the 50-target no more
doses on day 1
For those allocated the 100 mcg target delay
60 min and give 40 mcg
Visit 2
At 20 min intervals
For those allocated the 50-target 25 mcg + 25
mcg
For those allocated the 100-target 50 mcg + 50
mcg
Visit 3 Maintenance dose 50 mcg or 100 mcg
Semirush initiation
Visit 1At 20 min intervals 00001 mcg 0001 mcg
001 mcg
Visit 2 At 20 min intervals 001 01 mcg 03 mcg
Visit 3 At 30 min interval 03mcg 1mcg 3 mcg
Visit 4 At 30 min interval 3mcg 10 mcg
Visit 5 At 30 min interval 10mcg 20 mcg
Visit 6 At 30 min interval 20 mcg 30 mcg
Visit 7For those allocated the 50 mcg target (30 min
interval) 25 mcg 25 mcg
For those allocated the 100mcg (30 min
interval)30 mcg 40 mcg
Visit 8 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval) 50mcg 50 mcg
Visit 9 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval)70 mcg 30 mcg
Visit 10 Maintenance dose 50 mcg or 100 mcg
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
injections
LLR SR
Group A 199 0
Group B 32 09
Group C 36 056
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Patella V Florio G Giuliano A et al Hymenoptera Venom Immunotherapy Tolerance and Efficacy of an UltrarushProtocol versus a Rush and a Slow Conventional Protocol J Allergy (Cairo)20122012192192
P=027
3 Days Rush VIT
Day 1
1mcgmL
10 mcgmL
100 mcgmL
005 01 02 04 08 mL (005 01 02 04 08
mcg)
02 05 1 mL (2 5 10 mcg)
02 02 mL (20 20 mcg)
Day 2
100 mcgmL 02 03 05 mL (20 30 50 mcg)
Day 3
100 mcgmL 1 mL (100 mcg)
Conventional Regimen
1 mcgmL005 01 02 04 mL (005 01
02 04 mcg)
10 mcgmL005 01 02 04 mL (05 1 2 4
mcg)
100 mcgmL
002 005 007 01 02 04
06 08 1 ml (2 5 7 10 20 40
60 80 100 mcg)
Build-up of VIT
Goldberg A Yogev A Confino-Cohen R Three Days Rush Venom Immunotherapy in Bee Allergy Safe Inexpensive and
Instantaneously Effective Int Arch Allergy Immunol201115690-98
296 SRs
(BeegtV)
208SR
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Day Vial Volume (mL) Dosis (mcg)
1
1 01 01
1 02 02
1 04 04
1 08 08
2 02 2
2
2 04 4
2 08 8
3 01 10
3 02 20
3
3 04 40
3 06 60
3 08 80
3 1 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
48 patients
25 LR
2 patients mild SR
Saacutenchez-Morillas L Reantildeo Martos M Rodriacuteguez Mosquera M Iglesias Cadarso A Domiacutenguez Laacutezaro AR Safety of rushimmunotherapy with Hymenoptera venom Allergol Immunopathol (Madr) 200533(4)224-7 Spanish
Vial 1=1 mcgmLVial 2=10 mcgmL
Vial 3=100 mcgmL
Dose administered
(mcg)Time (min)
01 0
1 30
10 60
20 90
30 120
40 150
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Schiavino D Nucera E Pollastrini E De Pasquale T Buonomo A Bartolozzi F Lombardo C Roncallo C Patriarca G Specific ultrarush desensitization in Hymenoptera venom-allergic patients Ann Allergy Asthma Immunol 2004
Apr92(4)409-13
7 mildSRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Day Dose ml administered Mcgr administered Conc mcgml
1
1 010 001 01
2 010 01 1
3 010 1 10
4 020 2 10
2
5 030 3 10
6 035 35 10
7 035 35 10
3
8 010 10 100
9 015 15 100
10 015 15 100
4
11 020 20 100
12 025 25 100
13 025 25 100
5
14 030 30 100
15 035 35 100
16 035 35 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Bilograve MB Cinti B Brianzoni MF Braschi MC Bonifazi M Antonicelli LHoneybee venom immunotherapy a comparative study using purified and nonpurified aqueous extracts in patients with normal Basal serum tryptase concentrations J
Allergy (Cairo) 20122012869243
NPA275
PA25
Day DoseMcg
administeredinterval
1
1 01 30 min
2 1 30 min
3 10 30 min
4 20 30 min
5 30 60 min
6 50 60 min
7 7 100
14 8 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Roll A Hofbauer G Ballmer-Weber BK Schmid-Grendelmeier P Safety of specific immunotherapy using a four-hour ultra-rush induction scheme in bee and wasp allergy J
Investig Allergol Clin Immunol 200616(2)79-85
Injection
numberDose (mcg) Interval (min)
1 01 30
2 1 30
3 10 30
4 20 60
5 30 60
6 50 180
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Koumlhli-Wiesner A Stahlberger L Bieli C Stricker T Lauener R Induction of specific immunotherapy with hymenoptera venoms using ultrarush regimen in children safety and tolerance J Allergy (Cairo) 20122012790910
SR 29
SR 12
Ultrarush initiation
Visit 1
At 30 min intervals 01 mcg 1 mcg 3 mcg 10
mcg 20 mcg 30 mcg then
For those allocated the 50-target no more
doses on day 1
For those allocated the 100 mcg target delay
60 min and give 40 mcg
Visit 2
At 20 min intervals
For those allocated the 50-target 25 mcg + 25
mcg
For those allocated the 100-target 50 mcg + 50
mcg
Visit 3 Maintenance dose 50 mcg or 100 mcg
Semirush initiation
Visit 1At 20 min intervals 00001 mcg 0001 mcg
001 mcg
Visit 2 At 20 min intervals 001 01 mcg 03 mcg
Visit 3 At 30 min interval 03mcg 1mcg 3 mcg
Visit 4 At 30 min interval 3mcg 10 mcg
Visit 5 At 30 min interval 10mcg 20 mcg
Visit 6 At 30 min interval 20 mcg 30 mcg
Visit 7For those allocated the 50 mcg target (30 min
interval) 25 mcg 25 mcg
For those allocated the 100mcg (30 min
interval)30 mcg 40 mcg
Visit 8 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval) 50mcg 50 mcg
Visit 9 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval)70 mcg 30 mcg
Visit 10 Maintenance dose 50 mcg or 100 mcg
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
injections
LLR SR
Group A 199 0
Group B 32 09
Group C 36 056
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Patella V Florio G Giuliano A et al Hymenoptera Venom Immunotherapy Tolerance and Efficacy of an UltrarushProtocol versus a Rush and a Slow Conventional Protocol J Allergy (Cairo)20122012192192
P=027
3 Days Rush VIT
Day 1
1mcgmL
10 mcgmL
100 mcgmL
005 01 02 04 08 mL (005 01 02 04 08
mcg)
02 05 1 mL (2 5 10 mcg)
02 02 mL (20 20 mcg)
Day 2
100 mcgmL 02 03 05 mL (20 30 50 mcg)
Day 3
100 mcgmL 1 mL (100 mcg)
Conventional Regimen
1 mcgmL005 01 02 04 mL (005 01
02 04 mcg)
10 mcgmL005 01 02 04 mL (05 1 2 4
mcg)
100 mcgmL
002 005 007 01 02 04
06 08 1 ml (2 5 7 10 20 40
60 80 100 mcg)
Build-up of VIT
Goldberg A Yogev A Confino-Cohen R Three Days Rush Venom Immunotherapy in Bee Allergy Safe Inexpensive and
Instantaneously Effective Int Arch Allergy Immunol201115690-98
296 SRs
(BeegtV)
208SR
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Day Vial Volume (mL) Dosis (mcg)
1
1 01 01
1 02 02
1 04 04
1 08 08
2 02 2
2
2 04 4
2 08 8
3 01 10
3 02 20
3
3 04 40
3 06 60
3 08 80
3 1 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
48 patients
25 LR
2 patients mild SR
Saacutenchez-Morillas L Reantildeo Martos M Rodriacuteguez Mosquera M Iglesias Cadarso A Domiacutenguez Laacutezaro AR Safety of rushimmunotherapy with Hymenoptera venom Allergol Immunopathol (Madr) 200533(4)224-7 Spanish
Vial 1=1 mcgmLVial 2=10 mcgmL
Vial 3=100 mcgmL
Dose administered
(mcg)Time (min)
01 0
1 30
10 60
20 90
30 120
40 150
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Schiavino D Nucera E Pollastrini E De Pasquale T Buonomo A Bartolozzi F Lombardo C Roncallo C Patriarca G Specific ultrarush desensitization in Hymenoptera venom-allergic patients Ann Allergy Asthma Immunol 2004
Apr92(4)409-13
7 mildSRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Day DoseMcg
administeredinterval
1
1 01 30 min
2 1 30 min
3 10 30 min
4 20 30 min
5 30 60 min
6 50 60 min
7 7 100
14 8 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Roll A Hofbauer G Ballmer-Weber BK Schmid-Grendelmeier P Safety of specific immunotherapy using a four-hour ultra-rush induction scheme in bee and wasp allergy J
Investig Allergol Clin Immunol 200616(2)79-85
Injection
numberDose (mcg) Interval (min)
1 01 30
2 1 30
3 10 30
4 20 60
5 30 60
6 50 180
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Koumlhli-Wiesner A Stahlberger L Bieli C Stricker T Lauener R Induction of specific immunotherapy with hymenoptera venoms using ultrarush regimen in children safety and tolerance J Allergy (Cairo) 20122012790910
SR 29
SR 12
Ultrarush initiation
Visit 1
At 30 min intervals 01 mcg 1 mcg 3 mcg 10
mcg 20 mcg 30 mcg then
For those allocated the 50-target no more
doses on day 1
For those allocated the 100 mcg target delay
60 min and give 40 mcg
Visit 2
At 20 min intervals
For those allocated the 50-target 25 mcg + 25
mcg
For those allocated the 100-target 50 mcg + 50
mcg
Visit 3 Maintenance dose 50 mcg or 100 mcg
Semirush initiation
Visit 1At 20 min intervals 00001 mcg 0001 mcg
001 mcg
Visit 2 At 20 min intervals 001 01 mcg 03 mcg
Visit 3 At 30 min interval 03mcg 1mcg 3 mcg
Visit 4 At 30 min interval 3mcg 10 mcg
Visit 5 At 30 min interval 10mcg 20 mcg
Visit 6 At 30 min interval 20 mcg 30 mcg
Visit 7For those allocated the 50 mcg target (30 min
interval) 25 mcg 25 mcg
For those allocated the 100mcg (30 min
interval)30 mcg 40 mcg
Visit 8 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval) 50mcg 50 mcg
Visit 9 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval)70 mcg 30 mcg
Visit 10 Maintenance dose 50 mcg or 100 mcg
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
injections
LLR SR
Group A 199 0
Group B 32 09
Group C 36 056
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Patella V Florio G Giuliano A et al Hymenoptera Venom Immunotherapy Tolerance and Efficacy of an UltrarushProtocol versus a Rush and a Slow Conventional Protocol J Allergy (Cairo)20122012192192
P=027
3 Days Rush VIT
Day 1
1mcgmL
10 mcgmL
100 mcgmL
005 01 02 04 08 mL (005 01 02 04 08
mcg)
02 05 1 mL (2 5 10 mcg)
02 02 mL (20 20 mcg)
Day 2
100 mcgmL 02 03 05 mL (20 30 50 mcg)
Day 3
100 mcgmL 1 mL (100 mcg)
Conventional Regimen
1 mcgmL005 01 02 04 mL (005 01
02 04 mcg)
10 mcgmL005 01 02 04 mL (05 1 2 4
mcg)
100 mcgmL
002 005 007 01 02 04
06 08 1 ml (2 5 7 10 20 40
60 80 100 mcg)
Build-up of VIT
Goldberg A Yogev A Confino-Cohen R Three Days Rush Venom Immunotherapy in Bee Allergy Safe Inexpensive and
Instantaneously Effective Int Arch Allergy Immunol201115690-98
296 SRs
(BeegtV)
208SR
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Day Vial Volume (mL) Dosis (mcg)
1
1 01 01
1 02 02
1 04 04
1 08 08
2 02 2
2
2 04 4
2 08 8
3 01 10
3 02 20
3
3 04 40
3 06 60
3 08 80
3 1 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
48 patients
25 LR
2 patients mild SR
Saacutenchez-Morillas L Reantildeo Martos M Rodriacuteguez Mosquera M Iglesias Cadarso A Domiacutenguez Laacutezaro AR Safety of rushimmunotherapy with Hymenoptera venom Allergol Immunopathol (Madr) 200533(4)224-7 Spanish
Vial 1=1 mcgmLVial 2=10 mcgmL
Vial 3=100 mcgmL
Dose administered
(mcg)Time (min)
01 0
1 30
10 60
20 90
30 120
40 150
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Schiavino D Nucera E Pollastrini E De Pasquale T Buonomo A Bartolozzi F Lombardo C Roncallo C Patriarca G Specific ultrarush desensitization in Hymenoptera venom-allergic patients Ann Allergy Asthma Immunol 2004
Apr92(4)409-13
7 mildSRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Injection
numberDose (mcg) Interval (min)
1 01 30
2 1 30
3 10 30
4 20 60
5 30 60
6 50 180
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Koumlhli-Wiesner A Stahlberger L Bieli C Stricker T Lauener R Induction of specific immunotherapy with hymenoptera venoms using ultrarush regimen in children safety and tolerance J Allergy (Cairo) 20122012790910
SR 29
SR 12
Ultrarush initiation
Visit 1
At 30 min intervals 01 mcg 1 mcg 3 mcg 10
mcg 20 mcg 30 mcg then
For those allocated the 50-target no more
doses on day 1
For those allocated the 100 mcg target delay
60 min and give 40 mcg
Visit 2
At 20 min intervals
For those allocated the 50-target 25 mcg + 25
mcg
For those allocated the 100-target 50 mcg + 50
mcg
Visit 3 Maintenance dose 50 mcg or 100 mcg
Semirush initiation
Visit 1At 20 min intervals 00001 mcg 0001 mcg
001 mcg
Visit 2 At 20 min intervals 001 01 mcg 03 mcg
Visit 3 At 30 min interval 03mcg 1mcg 3 mcg
Visit 4 At 30 min interval 3mcg 10 mcg
Visit 5 At 30 min interval 10mcg 20 mcg
Visit 6 At 30 min interval 20 mcg 30 mcg
Visit 7For those allocated the 50 mcg target (30 min
interval) 25 mcg 25 mcg
For those allocated the 100mcg (30 min
interval)30 mcg 40 mcg
Visit 8 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval) 50mcg 50 mcg
Visit 9 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval)70 mcg 30 mcg
Visit 10 Maintenance dose 50 mcg or 100 mcg
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
injections
LLR SR
Group A 199 0
Group B 32 09
Group C 36 056
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Patella V Florio G Giuliano A et al Hymenoptera Venom Immunotherapy Tolerance and Efficacy of an UltrarushProtocol versus a Rush and a Slow Conventional Protocol J Allergy (Cairo)20122012192192
P=027
3 Days Rush VIT
Day 1
1mcgmL
10 mcgmL
100 mcgmL
005 01 02 04 08 mL (005 01 02 04 08
mcg)
02 05 1 mL (2 5 10 mcg)
02 02 mL (20 20 mcg)
Day 2
100 mcgmL 02 03 05 mL (20 30 50 mcg)
Day 3
100 mcgmL 1 mL (100 mcg)
Conventional Regimen
1 mcgmL005 01 02 04 mL (005 01
02 04 mcg)
10 mcgmL005 01 02 04 mL (05 1 2 4
mcg)
100 mcgmL
002 005 007 01 02 04
06 08 1 ml (2 5 7 10 20 40
60 80 100 mcg)
Build-up of VIT
Goldberg A Yogev A Confino-Cohen R Three Days Rush Venom Immunotherapy in Bee Allergy Safe Inexpensive and
Instantaneously Effective Int Arch Allergy Immunol201115690-98
296 SRs
(BeegtV)
208SR
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Day Vial Volume (mL) Dosis (mcg)
1
1 01 01
1 02 02
1 04 04
1 08 08
2 02 2
2
2 04 4
2 08 8
3 01 10
3 02 20
3
3 04 40
3 06 60
3 08 80
3 1 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
48 patients
25 LR
2 patients mild SR
Saacutenchez-Morillas L Reantildeo Martos M Rodriacuteguez Mosquera M Iglesias Cadarso A Domiacutenguez Laacutezaro AR Safety of rushimmunotherapy with Hymenoptera venom Allergol Immunopathol (Madr) 200533(4)224-7 Spanish
Vial 1=1 mcgmLVial 2=10 mcgmL
Vial 3=100 mcgmL
Dose administered
(mcg)Time (min)
01 0
1 30
10 60
20 90
30 120
40 150
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Schiavino D Nucera E Pollastrini E De Pasquale T Buonomo A Bartolozzi F Lombardo C Roncallo C Patriarca G Specific ultrarush desensitization in Hymenoptera venom-allergic patients Ann Allergy Asthma Immunol 2004
Apr92(4)409-13
7 mildSRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Ultrarush initiation
Visit 1
At 30 min intervals 01 mcg 1 mcg 3 mcg 10
mcg 20 mcg 30 mcg then
For those allocated the 50-target no more
doses on day 1
For those allocated the 100 mcg target delay
60 min and give 40 mcg
Visit 2
At 20 min intervals
For those allocated the 50-target 25 mcg + 25
mcg
For those allocated the 100-target 50 mcg + 50
mcg
Visit 3 Maintenance dose 50 mcg or 100 mcg
Semirush initiation
Visit 1At 20 min intervals 00001 mcg 0001 mcg
001 mcg
Visit 2 At 20 min intervals 001 01 mcg 03 mcg
Visit 3 At 30 min interval 03mcg 1mcg 3 mcg
Visit 4 At 30 min interval 3mcg 10 mcg
Visit 5 At 30 min interval 10mcg 20 mcg
Visit 6 At 30 min interval 20 mcg 30 mcg
Visit 7For those allocated the 50 mcg target (30 min
interval) 25 mcg 25 mcg
For those allocated the 100mcg (30 min
interval)30 mcg 40 mcg
Visit 8 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval) 50mcg 50 mcg
Visit 9 For those allocated the 50 mcg target 50 mcg
For those allocated the 100 mcg target (30 min
interval)70 mcg 30 mcg
Visit 10 Maintenance dose 50 mcg or 100 mcg
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
injections
LLR SR
Group A 199 0
Group B 32 09
Group C 36 056
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Patella V Florio G Giuliano A et al Hymenoptera Venom Immunotherapy Tolerance and Efficacy of an UltrarushProtocol versus a Rush and a Slow Conventional Protocol J Allergy (Cairo)20122012192192
P=027
3 Days Rush VIT
Day 1
1mcgmL
10 mcgmL
100 mcgmL
005 01 02 04 08 mL (005 01 02 04 08
mcg)
02 05 1 mL (2 5 10 mcg)
02 02 mL (20 20 mcg)
Day 2
100 mcgmL 02 03 05 mL (20 30 50 mcg)
Day 3
100 mcgmL 1 mL (100 mcg)
Conventional Regimen
1 mcgmL005 01 02 04 mL (005 01
02 04 mcg)
10 mcgmL005 01 02 04 mL (05 1 2 4
mcg)
100 mcgmL
002 005 007 01 02 04
06 08 1 ml (2 5 7 10 20 40
60 80 100 mcg)
Build-up of VIT
Goldberg A Yogev A Confino-Cohen R Three Days Rush Venom Immunotherapy in Bee Allergy Safe Inexpensive and
Instantaneously Effective Int Arch Allergy Immunol201115690-98
296 SRs
(BeegtV)
208SR
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Day Vial Volume (mL) Dosis (mcg)
1
1 01 01
1 02 02
1 04 04
1 08 08
2 02 2
2
2 04 4
2 08 8
3 01 10
3 02 20
3
3 04 40
3 06 60
3 08 80
3 1 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
48 patients
25 LR
2 patients mild SR
Saacutenchez-Morillas L Reantildeo Martos M Rodriacuteguez Mosquera M Iglesias Cadarso A Domiacutenguez Laacutezaro AR Safety of rushimmunotherapy with Hymenoptera venom Allergol Immunopathol (Madr) 200533(4)224-7 Spanish
Vial 1=1 mcgmLVial 2=10 mcgmL
Vial 3=100 mcgmL
Dose administered
(mcg)Time (min)
01 0
1 30
10 60
20 90
30 120
40 150
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Schiavino D Nucera E Pollastrini E De Pasquale T Buonomo A Bartolozzi F Lombardo C Roncallo C Patriarca G Specific ultrarush desensitization in Hymenoptera venom-allergic patients Ann Allergy Asthma Immunol 2004
Apr92(4)409-13
7 mildSRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Ultrarush Semirush
65 SRs(12 severe)
29 SRs(0 severe)
Brown SGWiese MD van Eeden P et al Ultrarush versus semirush initiation of insect venom immunotherapy a randomized controlled trial J Allergy Clin Immunol 2012 Jul130(1)162-8
injections
LLR SR
Group A 199 0
Group B 32 09
Group C 36 056
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Patella V Florio G Giuliano A et al Hymenoptera Venom Immunotherapy Tolerance and Efficacy of an UltrarushProtocol versus a Rush and a Slow Conventional Protocol J Allergy (Cairo)20122012192192
P=027
3 Days Rush VIT
Day 1
1mcgmL
10 mcgmL
100 mcgmL
005 01 02 04 08 mL (005 01 02 04 08
mcg)
02 05 1 mL (2 5 10 mcg)
02 02 mL (20 20 mcg)
Day 2
100 mcgmL 02 03 05 mL (20 30 50 mcg)
Day 3
100 mcgmL 1 mL (100 mcg)
Conventional Regimen
1 mcgmL005 01 02 04 mL (005 01
02 04 mcg)
10 mcgmL005 01 02 04 mL (05 1 2 4
mcg)
100 mcgmL
002 005 007 01 02 04
06 08 1 ml (2 5 7 10 20 40
60 80 100 mcg)
Build-up of VIT
Goldberg A Yogev A Confino-Cohen R Three Days Rush Venom Immunotherapy in Bee Allergy Safe Inexpensive and
Instantaneously Effective Int Arch Allergy Immunol201115690-98
296 SRs
(BeegtV)
208SR
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Day Vial Volume (mL) Dosis (mcg)
1
1 01 01
1 02 02
1 04 04
1 08 08
2 02 2
2
2 04 4
2 08 8
3 01 10
3 02 20
3
3 04 40
3 06 60
3 08 80
3 1 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
48 patients
25 LR
2 patients mild SR
Saacutenchez-Morillas L Reantildeo Martos M Rodriacuteguez Mosquera M Iglesias Cadarso A Domiacutenguez Laacutezaro AR Safety of rushimmunotherapy with Hymenoptera venom Allergol Immunopathol (Madr) 200533(4)224-7 Spanish
Vial 1=1 mcgmLVial 2=10 mcgmL
Vial 3=100 mcgmL
Dose administered
(mcg)Time (min)
01 0
1 30
10 60
20 90
30 120
40 150
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Schiavino D Nucera E Pollastrini E De Pasquale T Buonomo A Bartolozzi F Lombardo C Roncallo C Patriarca G Specific ultrarush desensitization in Hymenoptera venom-allergic patients Ann Allergy Asthma Immunol 2004
Apr92(4)409-13
7 mildSRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
injections
LLR SR
Group A 199 0
Group B 32 09
Group C 36 056
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Patella V Florio G Giuliano A et al Hymenoptera Venom Immunotherapy Tolerance and Efficacy of an UltrarushProtocol versus a Rush and a Slow Conventional Protocol J Allergy (Cairo)20122012192192
P=027
3 Days Rush VIT
Day 1
1mcgmL
10 mcgmL
100 mcgmL
005 01 02 04 08 mL (005 01 02 04 08
mcg)
02 05 1 mL (2 5 10 mcg)
02 02 mL (20 20 mcg)
Day 2
100 mcgmL 02 03 05 mL (20 30 50 mcg)
Day 3
100 mcgmL 1 mL (100 mcg)
Conventional Regimen
1 mcgmL005 01 02 04 mL (005 01
02 04 mcg)
10 mcgmL005 01 02 04 mL (05 1 2 4
mcg)
100 mcgmL
002 005 007 01 02 04
06 08 1 ml (2 5 7 10 20 40
60 80 100 mcg)
Build-up of VIT
Goldberg A Yogev A Confino-Cohen R Three Days Rush Venom Immunotherapy in Bee Allergy Safe Inexpensive and
Instantaneously Effective Int Arch Allergy Immunol201115690-98
296 SRs
(BeegtV)
208SR
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Day Vial Volume (mL) Dosis (mcg)
1
1 01 01
1 02 02
1 04 04
1 08 08
2 02 2
2
2 04 4
2 08 8
3 01 10
3 02 20
3
3 04 40
3 06 60
3 08 80
3 1 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
48 patients
25 LR
2 patients mild SR
Saacutenchez-Morillas L Reantildeo Martos M Rodriacuteguez Mosquera M Iglesias Cadarso A Domiacutenguez Laacutezaro AR Safety of rushimmunotherapy with Hymenoptera venom Allergol Immunopathol (Madr) 200533(4)224-7 Spanish
Vial 1=1 mcgmLVial 2=10 mcgmL
Vial 3=100 mcgmL
Dose administered
(mcg)Time (min)
01 0
1 30
10 60
20 90
30 120
40 150
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Schiavino D Nucera E Pollastrini E De Pasquale T Buonomo A Bartolozzi F Lombardo C Roncallo C Patriarca G Specific ultrarush desensitization in Hymenoptera venom-allergic patients Ann Allergy Asthma Immunol 2004
Apr92(4)409-13
7 mildSRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
3 Days Rush VIT
Day 1
1mcgmL
10 mcgmL
100 mcgmL
005 01 02 04 08 mL (005 01 02 04 08
mcg)
02 05 1 mL (2 5 10 mcg)
02 02 mL (20 20 mcg)
Day 2
100 mcgmL 02 03 05 mL (20 30 50 mcg)
Day 3
100 mcgmL 1 mL (100 mcg)
Conventional Regimen
1 mcgmL005 01 02 04 mL (005 01
02 04 mcg)
10 mcgmL005 01 02 04 mL (05 1 2 4
mcg)
100 mcgmL
002 005 007 01 02 04
06 08 1 ml (2 5 7 10 20 40
60 80 100 mcg)
Build-up of VIT
Goldberg A Yogev A Confino-Cohen R Three Days Rush Venom Immunotherapy in Bee Allergy Safe Inexpensive and
Instantaneously Effective Int Arch Allergy Immunol201115690-98
296 SRs
(BeegtV)
208SR
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Day Vial Volume (mL) Dosis (mcg)
1
1 01 01
1 02 02
1 04 04
1 08 08
2 02 2
2
2 04 4
2 08 8
3 01 10
3 02 20
3
3 04 40
3 06 60
3 08 80
3 1 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
48 patients
25 LR
2 patients mild SR
Saacutenchez-Morillas L Reantildeo Martos M Rodriacuteguez Mosquera M Iglesias Cadarso A Domiacutenguez Laacutezaro AR Safety of rushimmunotherapy with Hymenoptera venom Allergol Immunopathol (Madr) 200533(4)224-7 Spanish
Vial 1=1 mcgmLVial 2=10 mcgmL
Vial 3=100 mcgmL
Dose administered
(mcg)Time (min)
01 0
1 30
10 60
20 90
30 120
40 150
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Schiavino D Nucera E Pollastrini E De Pasquale T Buonomo A Bartolozzi F Lombardo C Roncallo C Patriarca G Specific ultrarush desensitization in Hymenoptera venom-allergic patients Ann Allergy Asthma Immunol 2004
Apr92(4)409-13
7 mildSRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Day Vial Volume (mL) Dosis (mcg)
1
1 01 01
1 02 02
1 04 04
1 08 08
2 02 2
2
2 04 4
2 08 8
3 01 10
3 02 20
3
3 04 40
3 06 60
3 08 80
3 1 100
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
48 patients
25 LR
2 patients mild SR
Saacutenchez-Morillas L Reantildeo Martos M Rodriacuteguez Mosquera M Iglesias Cadarso A Domiacutenguez Laacutezaro AR Safety of rushimmunotherapy with Hymenoptera venom Allergol Immunopathol (Madr) 200533(4)224-7 Spanish
Vial 1=1 mcgmLVial 2=10 mcgmL
Vial 3=100 mcgmL
Dose administered
(mcg)Time (min)
01 0
1 30
10 60
20 90
30 120
40 150
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Schiavino D Nucera E Pollastrini E De Pasquale T Buonomo A Bartolozzi F Lombardo C Roncallo C Patriarca G Specific ultrarush desensitization in Hymenoptera venom-allergic patients Ann Allergy Asthma Immunol 2004
Apr92(4)409-13
7 mildSRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Dose administered
(mcg)Time (min)
01 0
1 30
10 60
20 90
30 120
40 150
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
Schiavino D Nucera E Pollastrini E De Pasquale T Buonomo A Bartolozzi F Lombardo C Roncallo C Patriarca G Specific ultrarush desensitization in Hymenoptera venom-allergic patients Ann Allergy Asthma Immunol 2004
Apr92(4)409-13
7 mildSRs
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Efficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Build-up of VIT
SEAIC 3 weeks Protocol
Day Vialml Doseml Dosemcgr
1
3 05 5
4 01 10
4 02 20
4 02 20
84 05 50
4 05 50
22 4 1 100
SEAIC 4 weeks Protocol
Day Vialml Doseml Dosemcgr
13 05 5
4 01 10
84 02 20
4 03 30
15
4 05 50
4 05 50
22 4 1 100
SEAIC 9 weeks Protocol
Week Vialml Doseml Dosemcgr
1 2 01 01
2 3 01 1
3 3 05 5
4 4 01 10
5 4 02 20
6 4 04 40
7 4 06 60
8 4 08 80
9 4 1 100
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
bull Mediterranean Vespula germanica amp Polistesdominulus evenly distributed Double sensitization is frequent
bull 37 patients
ndash 8 LLR
ndash Vespula 075 per dose
ndash Polistes 045 per dose
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Initiation Phase
Day Dose (Mcg)
1
10
20
20
750
50
Build-up of VITEfficacy amp Tolerance
Pretreatment ConclusionsExtractsTailor-madeBackground
Moreno C Barasona MJ Serrano P Justicia JL Ruz JM Guerra F Alternating Polistes-Vespula venom immunotherapy a therapeutic strategy to resolve a diagnostic deficiency J Investig Allergol Clin Immunol
201121(1)28-33
Polistes Even months
Vespula Odd months
Maintenance Phase
Re-sting All Negative
8 LLRVespula 075 per dosePolistes 045 per dose
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
bull Large EAACI multicenter study side-effects
bull Buildup Median dose of 30 mcg (range 001-150)
bull Very mild 13 required treatment
bull Female sex
bull Rapid dose-increase regimens
bull Bee-venom extract
bull Pre-existing allergic rhinitis
Tailor-made Pretreatment ConclusionsExtractsEfficacy amp Tolerance
Background
Build-up of VIT
Mosbech H Muumlller U Side-effects of insect venom immunotherapy results from an EAACI multicenter study European Academy of Allergology and Clinical Immunology Allergy 2000 Nov55(11)1005-10
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
bull Much lower rate of discontinuation of VIT
bull uarrefficacy VIT inhibition of T helper type 2 cytokine production
bull uarrpatient comfort
bull 180 mg fexofenadine
ndash darrLLRs (64 vs 89) plt005)
ndash Mild SRs (affecting only the skin) (4 vs 23 plt005)
Reimers A Hari Y Muller U Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine a double-blind placebo-controlled trial Allergy 2000 55484-488
bull Anti-IgE more rapid and uarrdoses
Efficacy amp Tolerance
ConclusionsExtractsBackground PretreatmentTailor-made
Build-up of VIT
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Purified Aqueous Non Purified Aqueous
Vasoactive aminesDA 5-HT Histamine
NO Yes
Apamine kinins mastcell degranulating
peptidedarr uarr
SR 2 6
LLR 9 24
Total Reactions(SR+LLR)
11 (09 of injections)
30 (27 of injections)
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Bilograve MB Severino M Cilia M et al The VISYT trial Venom Immunotherapy Safety and Tolerability with purified vs nonpurified extracts Ann Allergy Asthma Immunol 2009
Jul103(1)57-61
P=057
P=002
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Induction Phase (Aqueous)
Week Vial Dose mcgmL Time (h)Amount
administered mcL
Amount
administered
mcg
1 1 1 01 0 01 001
1 2 2 10 05 01 01
1 3 3 10 1 01 10
1 3 4 10 15 03 35
2 3 5 10 0 05 50
2 3 6 10 05 05 50
3 4 7 100 0 01 10
3 4 8 100 05 01 10
4 4 9 100 0 02 20
4 4 10 100 05 02 20
5 4 11 100 0 035 35
5 4 12 100 05 035 35
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Adverse Effects
49
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Induction Phase (Depot)
Week Vial Dose mcgmL Time (h)
Amount
administered
mcL
Amount
administered mcg
1 1 1 01 0 03 003
1 1 2 01 05 10 01
1 2 3 10 1 03 03
1 2 4 10 15 10 10
2 3 5 10 0 02 2
2 3 6 10 05 04 4
3 3 7 10 0 06 6
3 3 8 10 05 10 10
4 4 9 100 0 01 10
4 4 10 100 05 02 20
5 4 11 100 0 03 30
5 4 12 100 05 03 30
6 4 13 100 0 05 50
6 4 14 100 03 05 50
Efficacy amp Tolerance
ConclusionsBackground Tailor-made Pretreatment Extracts
Build-up of VIT
Alessandrini AE Berra D Rizzini FL et al Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy Ann Allergy Asthma Immunol 2006 Jul97(1)92-7
Adverse Effects
118 (17 per dose)
AqueousAdverse
Effects 49 (59 per
dose)
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
bull A great deal of induction regimens Heterogeneity
bull Controversy about cumulative dose
bull The number of injections incidence of SR (plt0001)
bull Purified extracts better than NPAdarrLLR
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull Female sex uarrBTC rapid dose-increase regimens bee-venom extract and pre-existing allergic rhinitis other treatments and comorbidities uarr side effects
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
bull The rate of systemic reactions in rush VIT decreases with the reduction of the cumulative venom dose
bull The frequency and the severity of local reactions are reduced with pretreatment uarr patient comfort
bull Pretreatment darrdiscontinuation of VIT and uarr efficacy
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Pros Cons
Surveillance
ConclusionsEfficacy amp Tolerance
Background Tailor-made Pretreatment Extracts
Build-up of VIT
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Pretreatment
Extract
Patient
Build-up of VIT
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
Thank you
Mercedes Rodriacuteguez-Rodriacuteguez
Mariacutea Joseacute Saacutenchez-Gonzaacutelez
Joseacute Barbarroja-Escudero
Melchor Aacutelvarez-Mon Soto
Hymenoptera Venom Hypersensitivity Committee of the SEAIC
