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Efficacy of immunotherapy and symptomatic drugs

Speaker: Paolo M Matricardi

29 September 2012


The 9° Symposium on Specific Allergy Berlin – September 27-29, 2012

Efficacy of Immunotherapy and Symptomatic Drugs

Paolo M. Matricardi, MD, PD

Dept. of Paediatric Pneumology and Immunology Charité Medical School, Berlin, Germany


Declaration of potential conflict of interest Between 2011 and 2012 P.M. Matricardi has received research grants and/or honoraria from public or private institutions, including: Alk-Abello Allergopharma German Research Foundation (DFG) Stallergenes TFS TPS


Background

SCIT, a second line in SAR? Allergen-specific subcutaneous immunotherapy SCIT of seasonal allergic rhinitis (SAR) is usually considered a “second-line�, slow-acting, disease-modifying treatment,

Many doctors would agree with the statement that SCIT should be proposed only when anti-symptomatic treatment with drugs is not: 1) effective 2) accepted 3) tolerated


Working Hypothesis

Is SCIT really less effective than drugs in SAR in the first season after treatment initiation?


Methods 1. 2. 3. 4.

Categories examined: SCIT, anti-AH1, NCS, LA, Only studies already included in a peer-reviewed meta-analyses Only meta-analyses with at least 5 studies (aug-oct 2009) Two primary outcomes: TNSS = total nasal symptom score TSS = total symptom score (nasal, eye, bronchi) 5. Two measures for the effect size: RCI = relative clinical impact (% effect over placebo) SMD = standardized mean difference


SCIT 25

300

250

10

250

8

200

6

150

4

100

50

2

50

0

0

150 10 100

April

May

June

July

August

Pollen grains count

12

200

0

Treatment period

300

15

5

Trials of Anti-symptomatic drugs Baseline period

Pollen grains counts

20

Symptoms score

B

Trials of SCIT Observation during the whole pollen season

Symptoms score

A

DRUGS

0 April

Pollen counts Verum Placebo

May

June

July

Pollen grains count Anti-symptomatic treatment Placebo

vs

August


STUDIES INCLUDED IN THE ANALYSIS

SCIT

SCIT

Calderon Cochrane Rev 2007

LA

Rodrigo

NCS

Penagos

AH1

Canonica

AAAI 2006

Allergy 2008

Allergy 2007

TREATMENT OUTCOME

STUDIES (ex/incl)

STUDIES analysed

Pollen

TSS TNSS

276 ; 15 276 ; 8

12 6

Montelukast

TNSS

76 ; 17

6

Mometasone

TNSS

242 ; 16

8

Desloratadine

TSS

229 ; 13

6


SCIT - TSS Calderon et al. Cochrane Rev. 2007


SCIT - TNSS Calderon et al. Cochrane Rev. 2007


Montelukast (LA) - TNSS Rodrigo et al. Annals Allergy Asthma Immunol. 2006


Desloratadine (AH-1) - TSS Canonica et al. Allergy. 2007


Mometasone (NCS) - TNSS Penagos et al. Allergy. 2008


SCIT vs Drugs RCI

SMD

a

b

TSS

SMD, 95% CI

Desloratadine p<0.001

TSS

(525 vs 530) (6)

SCIT

Desloratadine (525 vs 530) (6)

SCIT (474 vs 348) (12)

(474 vs 348) (12)

-2 0

-5

-10 TSS

-15

-20

-25

-30

-35

0 favours active

-40

2 favours placebo

RCI over placebo (%)

d

c

TNSS

SMD, 95% CI (1584 vs 1577) (6)

p<0.001

(783 vs 716) (8)

SCIT (349 vs 236) (6)

p<0.001

Mometasone

TNSS

Montelukast Montelukast (1584 vs 1577) (6)

Mometasone (783 vs 716) (8)

SCIT

(349 vs 236) (6)

-2 0

-5

-10 -15 -20 -25 -30 TNSS RCI over placebo (%)

-35

-40

0 favours active

2 favours placebo


LIMITATIONS

vs

????


PUTATIVE LIMITATIONS 1) efficacy measures appropriate and validated?

2) trials homogeneous enough? 3) different use of rescue medications? A bias in favor of SCIT? 4) differences in the population size? 5) differences in the follow-up duration (whole vs peak season)? 6) differences in disease severity?


PUTATIVE LIMITATIONS •

efficacy measures appropriate and validated? - RCI = WAO, SMD = Cochrane

trials homogeneous enough? A) SCIT and Drug trials from a Cochrane and Peer reviewed M B) SCIT trials different pollens but similar results for grass only C) SCIT vs Drug trials = heterogeneous categories

different use of rescue medications? A bias in favor of SCIT? less drugs in SCIT vs placebo treated

differences in the population size? when comparing only large trials same conclusions

differences in the follow-up duration (whole vs peak season)? even stronger difference in peak season for SCIT

differences in disease severity? SCIT trials more severe: higher possibility of improvement? or patients less susceptible to improvement?


A TSS

Magnitude of Effect

loratadine

(739 vs 601)

desloratadine

(164 vs 164)

Only large Trials (n>100)

ebastine

(749 vs 601)

fexofenadine

(463 vs 469)

SCIT

(187 vs 89) 0%

-10%

-20%

-30%

-40%

-50%

% RCI [100*(score active-score placebo)/score placebo]

B (135 vs 136)

mometasone

(151 vs 148)

fluticasone

TNSS

ciclesonide

(164 vs 163)

montelukast

(522 vs 521)

SCIT

(187 vs 89) 0%

-10%

-20%

-30%

-40%

% RCI [100*(score active-score placebo)/score placebo]

-50%


conclusions indirect but intriguing evidence that:

1. SCIT is an anti-symptomatic treatment in Seasonal Allergic Rhinconjunctivitis (SAR) 2. at least as potent as drugs even in the first season of treatment ---------------Clinical implications? Many other factors contribute to therapeutic choices: e.g. safety, costs, long-term efficacy, compliance, prevention -----------------

direct evidence? = need a new trial


Acknowledgements Piotr Kuna, Univ. of Lodz Poland

Ulrich Wahn, Charitè Med School Berlin, Germany

Valentina Panetta, IRCSS Fatebenefratelli Rome, Italy (statistician)

Moises Calderon for permission to use Cochrane data

Annemie Narkus, Sabine Mussler Allergopharma Reinbeck, Germany

Paolo M Matricardi  
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