Use of Multiple Allergen Mixes in Immunotherapy
Harold S. Nelson, MD
Professor of Medicine
National Jewish Health
University of Colorado Denver School of Medicine,
Denver, Colorado, USA
Studies of the Use of ≥ 2 Allergens in Immunotherapy
Reviewed English & non-English literature 1961-2007:
4 studies with 2-allergen mixes (SCIT & SLIT):Results > placebo and = to single allergen when reported.
6 studies with > 2 allergen mixes (all SCIT):4 showed clinical efficacy (2 asthma, 2 rhinitis.2 failed to show clinical efficacy.
HS Nelson. J Allergy Clin Immunol 2009;123:763-0
The Value of Hyposensitization Therapy for Bronchial Asthma in Children -A 14-year Study
Subjects: Every child with perennial bronchial asthma and positive skin tests referred to the pediatric allergy clinic of Strong Memorial Hospital between August 1953 and January 1955.
Randomly assigned to receive injections of saline, extract 10-7 , 1/5,000 or 1/250 w/v concentration of all skin test positive inhalant allergens.
DE Johnstone, A Dutton Pediatrics 1968l42:793-802
The Value of Hyposensitization Therapy for Bronchial Asthma in Children - A 14-year Study
Parents did not know they were in a study, those evaluating the patients were unaware of which group the child was in.
230 enrolled,173 still in study after 4 years and 130 competed the study on reaching age 16 years.
Similar numbers dropped out of each treatment group.
DE Johnstone, A Dutton Pediatrics 1968l42:793-802
The Value of Hyposensitization Therapy for Bronchial Asthma in Children - A 14-year Study
“Free of Asthma” After 4 years- placebo and lowest dose 18%- 1/5,000 w/v 58%- 1/250 w/v 81%
“Free of Asthma” at end of study (age 16 yr)- placebo and lowest dose 22%- 1/5,000 w/v 66%- 1/250 w/v 78%
DE Johnstone, A Dutton Pediatrics 1968l42:793-802
A Double-blind Study of the Effectiveness and Specificity of Injection
Therapy in Ragweed Hay Fever
Patients were matched for symptom scores during the ragweed pollen season of 1962.
Patients were receiving injections with ragweed plus other allergens.
In March 1963 caramelized sugar was substituted for ragweed extract in one of each pair.
Symptoms & medication scored during 1963 ragweed season.
FC Lowell & W Franklin. N. Engl J Med1965;273:675-9
Effectiveness and Specificity of Ragweed Immunotherapy
1200
800
400
0
19 26 2 9 16 23 30 7 14 21 28* * ** * * *
Aug. Sept. Oct.
treated untreated median mean
1963
To
tal
Sco
re
Lowell & Franklin NEJM 1965
Comparison of Two Dosages of Ragweed Extract in the Treatment of Pollenosis
Same study design. Ragweed content was reduced 95% in the
extract of one of each matched pair of subjects.
W Franklin & FC Lowell. JAMA 1967;201:915-7
1964 Aug. Sept. Oct.
Sym
pto
m a
nd
Sev
erit
y S
core
300
200
100
0
low dosehigh dose
mean median
* ** **
6 2012 27 3 ?10 17 24 3
Comparison of Two Doses of Ragweed Extract
W Franklin, FC Lowell JAMA 1967;201;915
Seasonal Asthma in Northern California: Allergic Causes and Efficacy of
Immunotherapy
18 grass-allergic subjects received pre- and co-seasonal injections of allergen extracts, 9 with placebo and 9 with grass pollen extract.
2-10 other allergens were included in each patients treatment extract.
Projected maintenance dose of grass contained 9.3 mcg of Gp 1 allergen.
MJ Reid, et al. J Allergy Clin Immunol 1986;78:590-600
8
6
4
2
0
1985ASTHMA
ME
AN
SM
S
Grass treatedNon-grass treated
25
20
15
10
0
RHINITISM
EA
N S
MS
Grass treatedNon-grass treated
300
200
100
0
CO
UN
TS
/cm
2
Grass pollen count
APRIL MAY JUNE
MONTHS
5
Response to Grass Subcutaneous I.T.
P < 0.05
P = 0.11
MJ Reid, et al. J Allergy Clin Immunol 1986;78:590-600
N = 9
N = 9
Evidence for Effectiveness of Immunotherapy Employing
Multiple Allergens Johnstone included all allergens to which the child
was skin test positive. He demonstrated a dose dependent improvement in asthma.
Lowell & Franklin removed or reduced only ragweed in patients’ multi-allergen mixture and demonstrated increased symptoms during the ragweed pollen season.
Reid added only grass or placebo to multiple allergen mixes and showed significant reduction in asthma symptoms during the grass pollen season.
Sheila M. Amar, MD, Ronald J. Harbeck, PhD, Michael Sills, BS, Lori J. Silveira, MS, Holly
O’Brien, RN, Harold S. Nelson, MD National Jewish Health,
J Allergy Clin Immunol 2009;121:
Single-center, randomized, double-blind, placebo-controlled
SLIT for 10 months, 56 subjects randomized to 3 arms- SLIT with timothy pollen extract alone (17
mcg Phl p 5 daily)- SLIT with same dose of timothy extract + 9
additional pollen extracts- SLIT placebo
TM Group, Allergen Extract
Amount
Timothy 1.0 mL
Diluent 9.0 mL
Caramelized Sugar
Placebo Group Amount
Diluent 10 mL
Caramelized Sugar
*Amount added to 10 ml vial for 1 month of treatment
*CMD : Timothy approximately 30x SCIT dose (17 mcg Phl p 5 qday), other allergens 15-20x SCIT dose
MAT Group, Allergen Extract
Amount
Timothy 1.0 mL
Maple, Box-Elder 1.0 mL
Ash, White 1.0 mL
Juniper, Western 1.0 mL
Elm, American 1.0 mL
Cottonwood, Common 1.0 mL
Firebush (Kochia) 1.0 mL
Ragweed, Western 1.0 mL
Sagebrush, Common 1.0 mL
Russian Thistle 1.0 mL
Multi-allergen Sublingual Immunotherapy:Results
Only 3 “ of rain fell in Denver the first 6 months of 2008
Accordingly there was little grass pollen, few symptoms and no difference in symptom scores or medication use among the three treatment groups.
There were, however, significant differences in several clinically relevant outcomes.
p=0.03
p=0.001
p=0.04
p=0.005
Evidence for Effectiveness of Immunotherapy Employing
Multiple Allergens: Conclusions
Four studies support the effectiveness of subcutaneous immunotherapy employing multiple allergens.
The only study of multiple allergen sublingual immunotherapy raises questions regarding its effectiveness.