ALLERGIC RHINITIS: Evidence Based Medicine - Confex · •Of 2152 identified articles, 20 were...

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

ThankThank YouYou

canonica@unige.it canonica@unige.it