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Prof.Giorgio Walter CanonicaAllergy and Respiratory Diseases Department
University of Genoa
Cancun, December 5, 2011
Past President 1°vice President
ALLERGIC RHINITIS:ALLERGIC RHINITIS:EvidenceEvidence BasedBased MedicineMedicine
‐ Chiesi Farmaceutici‐ Danone‐ Faes‐ Glaxo Smith Kline‐ Hal‐ Lallemand‐ Lofarma‐Merck Sharp & Dome‐ Nycomed Takeda‐ Novartis
‐ Pfizer‐ Sanofi‐ SigmaTau‐ Stallergenes‐ Thermo Fisher‐ URIACH‐ Valeas
Prof. Giorgio Walter CANONICA , in the last five years, has been:‐scientific consultant as a single scientist or in national/international boards,‐researcher in scientific trials in his university or in collaboration with other research institutions, ‐speaker in scientific meetings, seminars and educational activities devoted to specialists, general practitioners and other healthcare professionals,totally or partially supported by the following commercial companies:
-A.Menarini-Alk-Abello’-Almirall-Allergy Therapeutics-Anallergo-AstraZeneca-Boeringher Ingelheim
Opinion Opinion BasedBased MedicineMedicine
BousquetBousquet J. J. etet al.,al.,AllergyAllergy 2004 2004
POSITION PAPER POSITION PAPER ITALIAN SOCIETY of ALLERGY ITALIAN SOCIETY of ALLERGY & & CLINICAL IMMUNOLOGYCLINICAL IMMUNOLOGY
IMMUNOTERAPIA SPECIFICA delle ALLERGIEIMMUNOTERAPIA SPECIFICA delle ALLERGIE
19911991
SLITSLIT::
……………………………………………….. .. RiskRisk of severe of severe reactionsreactions
DUE TO THE RAPID ABSORPTIONDUE TO THE RAPID ABSORPTIONof the of the allergenallergen………………....
Opinion Opinion BasedBased MedicineMedicine
Absorption and Absorption and distribution kinetics of distribution kinetics of the major the major ParietariaParietariaJudaicaJudaica (Par J 1)(Par J 1)allergen administered by allergen administered by nonnon--injectable to healthy injectable to healthy humans beings.humans beings.
M.BagnascoM.Bagnasco, , G.MarianiG.Mariani, , G.PassalacquaG.Passalacqua, , C.MottaC.Motta, , M.BartolomeiM.Bartolomei, P. , P. FalagianiFalagiani, , G.MistrelloG.Mistrello, G.W. Canonica, G.W. Canonica
JACI 1997; 100:199JACI 1997; 100:199
5 10 15 20 2h 2h 5h 20h30
0
1
2
3
4
5
60
Subl 1Subl 2Subl 3OralNasal
time after administration
plas
ma
radi
oact
ivity
% dose/liter 123I-Pr j l:alternative routes
swallow
BagnascoBagnasco etet al.al. J.A.C.I.J.A.C.I. 19971997
Pharmacokinetics of anPharmacokinetics of anallergen and a allergen and a MonomericMonomericAllergoidAllergoid for for oromucosaloromucosalimmunotherapy in allergic immunotherapy in allergic volunteersvolunteers
Bagnasco M., et al
ClinClin Exp.AllergyExp.Allergy 20012001
DerDer p1 p1 monomericmonomeric allergoidallergoid. Allergic volunteer
E.B.M.E.B.M.EvidenceEvidence BasedBased MedicineMedicine
Compalati 09
Guyatt GHACP J Club 1991 Mar‐Apr
11
20 years20 years
Mildpersistent
ARIA Guidelines: Recommendationsfor Management of Allergic Rhinitis
Mildintermittent
Moderate/severe
intermittent
Moderate/severe
persistent
Consider immunotherapy
Allergen and irritant avoidance
Intranasal decongestant (<10 days) or oral decongestant
Second‐generation nonsedating H1‐antihistamine
Leukotriene receptor antagonists
Local chromone
Intranasal corticosteroid
Check for asthma
Bousquet et al. J Allergy Clin Immunol. 2001;108(5 suppl):S147. At: http://www.whiar.org.
Strength of Evidence for Treatmentof Rhinitis: ARIA 2008
Bousquet et al. Allergy. 2008;63(suppl 86):8.
Intervention Adult Children Adult Children
Oral anti‐H1 A A A A
Intranasal anti‐H1 A A A A
Intranasal CS A A A A
Intranasal chromone A A A A
Antileukotriene A A B
Subcutaneous SIT A A A A
Sublingual/nasal SIT B A A A B
Allergen avoidance D D D B
IAR PER
JACI 2001
Bousquet J. et al.,Allergy 2004
From EBM to recommendation
Evidence‐based medicine
Clinical recommendationson efficacy for an intervention
ConclusionsQualityGraphicsProceduresPrinciplesBackground
Shekelle BMJ 1999; 318; 593-596 Università degli Studi di Genova
metanalysismetanalysis
Opinion BasedOpinion Based
EAACI/GA2LEN/EDF Guidelines for Management of Urticaria
Zuberbier et al. Allergy. 2006;61:321‐331.
EAACI / WAO / GA2LEN / EDF Guidelines
Urticaria 20083rd International Consensus Meeting on Urticaria
2009
ARIA/EAACI Requirements for Antihistamines in the Treatment of AR
Bousquet. Allergy. 2003;58:192.Bousquet. Allergy. 2004;59(suppl 77):4.Bousquet et al. Allergy. 2008;63(suppl 86):8.
Case Report, Ideas
Editorials, Expert Opinion
Cohort Studies
Case series
Meta-analisis andSystematic reviews
RandomizedDBPC
EBM Hierarchy
D
A
DrDr.Cochrane.Cochrane
GUIDELINES
www.pubmed.com Università degli Studi di Genova
ConclusionsQualityGraphicsProceduresPrinciplesBackground
www.pubmed.com Università degli Studi di Genova
ConclusionsQualityGraphicsProceduresPrinciplesBackground
0
500
1000
1500
2000
2500
3000
3500
4000
4500
93-94 94-95 95-96 96-97 97-98 98-99 99-00 00-01 01-02 02-03 03-04 04-05 05-06
NumberNumber of of PublishedPublished MetanalysisMetanalysis StudiesStudies
METANALYSIS METANALYSIS -- ForrestForrest PlotPlot
NONO
OUTOUT
GOAL!!!!GOAL!!!!
Systematic review on the efficacy of fexofenadine in seasonal allergic rhinitis: a meta‐analysis of randomized, double‐blind,
placebo‐controlled clinical trials.
2011
• All double‐blind, placebo‐controlled randomized trials assessing the efficacy of fexofenadine in AR were searched in OVID, MEDLINE, EMBASE databases up to December 2007
• Outcomes were extracted from original articles; when this information was not available, authors of each trial were contacted
• Some graphics were digitalized. RevMan 5 program was used to perform the analysis.
• GradePro 3.2.2 was used to assess the quality of the evidence for paediatric population.
• Of 2152 identified articles, 20 were potentially relevant trials. Eight studies satisfied inclusion criteria and were included in the meta‐analysis. The main reasons for exclusion were: not natural exposition, strong study limitations, atypical outcome measurement, design for other outcomes, not placebo‐controlled, single blind studies. Seven trials investigated a mixed population of adults and
children, one only children and one only adults.
• In 1,833 patients receiving fexofenadine
• 1,699 placebo
Is it GOAL???????????
You should use the funnel plot to investigate the presence of publication bias in your review
The horizontal axis measures the treatment effect
The point estimate from each study is then plotted…
…a vertical line added, where the pooled estimate from the meta‐analysis lies
more precise studies
lessless precise precise studiesstudies
There are some statistical tests for detecting funnel plot asymmetry:
‐ Egger's linear regression test‐ Begg's rank correlation test
12‐24 h reflective TSS
This study has five major aspects: it represents the first attempt to evaluate the efficacy and safety of fexofenadine in the treatment of AR by means of meta‐analysis of RCTs;
• Consistency between positive results in terms of efficacy in TSS and in individual symptoms;
• Large population studied;
• Not relevant inter‐study heterogeneity;
• Adverse events frequency was similar in both groups (placebo).
All these values encourage the recommendation
of fexofenadine for AR.
Treatment of allergic rhinitis (ARIA)Treatment of allergic rhinitis (ARIA)Allergic Rhinitis and its Impact on AsthmaAllergic Rhinitis and its Impact on Asthma
mildintermittent
mildpersistentmoderate
severeintermittent
moderatesevere
persistent
allergen and irritant avoidance
immunotherapy
intra‐nasal decongestant (<10 days) or oral decongestant
local cromoneintra‐nasal steroid
oral or local non‐sedative H1‐blocker
A A generalgeneral processprocess in in guidelinesguidelines evolutionevolution
J.A.C.I. September 2010
Brozek et al.,J.A.C.I. September 2010
Interpretation of Recommendations
Brozek et al.,J.A.C.I. September 2010
Antihistamines
Weak: 84%
Very lowStrength of
recommendation
2010
Moderate
Low
Very low
Grade ofevidence
2010
Brozek et al.,J.A.C.I. September 2010
Clinical Implications
FEXOFENADINE
Is fulfilling the ARIA criteria Is fulfilling the ARIA criteria for Antifor Anti‐‐H1H1
Is fulfilling the ARIAIs fulfilling the ARIA‐‐GRADEGRADErecommendationsrecommendations
FEXOFENADINE
RanksRanks at the Top at the Top in in E.B.M.E.B.M.
ELECTRONIC MEDICAL RECORD
STANFORD INTEGRATED DATABASE ENVIROMENT
NERO WOLFEby Rex Stout
SO…WE CAN TREAT PROPERLY ALSO THE BIG NOSES
SO…WE CAN TREAT PROPERLY ALSO THE BIG NOSES
