Placebo effects in allergen immunotherapy-An EAACI Task Force Position Paper.
Oliver Pfaar
(1)
,
Ioana Agache
(2)
,
Karl-Christian Bergmann
(3, 4)
,
Carsten Bindslev-Jensen
(5)
,
Jean Bousquet
(6, 7)
,
Peter Creticos
(8)
,
Philippe Devillier
(9, 10)
,
Stephen Durham
(11)
,
Peter Hellings
(12, 13, 14)
,
Susanne Kaul
(15)
,
Jörg Kleine-Tebbe
(16)
,
Ludger Klimek
(17)
,
Lars Jacobsen
(18)
,
Marek Jutel
(19)
,
Antonella Muraro
(20)
,
Nikolaos Papadopoulos
(21, 22)
,
Winfried Rief
(1)
,
Glenis Scadding
(23)
,
Manfred Schedlowski
(24)
,
Mohamed Shamji
(11)
,
Gunter Sturm
(25, 26)
,
Ronald van Ree
(27)
,
Carmen Vidal
(28)
,
Stefan Vieths
(15)
,
Bettina Wedi
(29)
,
Roy Gerth van Wijk
(30)
,
Anthony Frew
(31, 32)
1
Philipps Universität Marburg = Philipps University of Marburg
2 Transylvania University of Brasov
3 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
4 BIH - Berlin Institute of Health
5 OUH - Odense University Hospital
6 UM - Université de Montpellier
7 MACVIA-LR - Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon
8 Johns Hopkins University School of Medicine [Baltimore]
9 Hôpital Foch [Suresnes]
10 Université Paris-Saclay
11 Imperial College London
12 University Hospitals Leuven [Leuven]
13 UvA - University of Amsterdam [Amsterdam] = Universiteit van Amsterdam
14 UGENT - Universiteit Gent = Ghent University
15 EPI - Paul-Ehrlich-Institute - Federal Institute for Vaccines and Biomedicines
16 AAZW - Allergy and Asthma Center Westend
17 Center for Rhinology and Allergology = Zentrum für Rhinologie und Allergologie
18 Allergy Learning and Consulting
19 Wrocław Medical University
20 AOUP - Azienda Ospedale Università di Padova = Hospital-University of Padua
21 University of Manchester [Manchester]
22 University of Athens, Athens
23 UCLH - University College London Hospitals
24 Institute of Medical Psychology and Behavioral Immunobiology
25 Medical University of Graz
26 Allergy Outpatient Clinic Reumannplatz
27 Amsterdam UMC - Amsterdam University Medical Center
28 USC - Universidade de Santiago de Compostela [Spain]
29 MHH - Medizinische Hochschule Hannover = Hannover Medical School
30 Erasmus MC - Erasmus University Medical Center [Rotterdam]
31 University of Sussex
32 University of Brighton
2 Transylvania University of Brasov
3 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
4 BIH - Berlin Institute of Health
5 OUH - Odense University Hospital
6 UM - Université de Montpellier
7 MACVIA-LR - Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon
8 Johns Hopkins University School of Medicine [Baltimore]
9 Hôpital Foch [Suresnes]
10 Université Paris-Saclay
11 Imperial College London
12 University Hospitals Leuven [Leuven]
13 UvA - University of Amsterdam [Amsterdam] = Universiteit van Amsterdam
14 UGENT - Universiteit Gent = Ghent University
15 EPI - Paul-Ehrlich-Institute - Federal Institute for Vaccines and Biomedicines
16 AAZW - Allergy and Asthma Center Westend
17 Center for Rhinology and Allergology = Zentrum für Rhinologie und Allergologie
18 Allergy Learning and Consulting
19 Wrocław Medical University
20 AOUP - Azienda Ospedale Università di Padova = Hospital-University of Padua
21 University of Manchester [Manchester]
22 University of Athens, Athens
23 UCLH - University College London Hospitals
24 Institute of Medical Psychology and Behavioral Immunobiology
25 Medical University of Graz
26 Allergy Outpatient Clinic Reumannplatz
27 Amsterdam UMC - Amsterdam University Medical Center
28 USC - Universidade de Santiago de Compostela [Spain]
29 MHH - Medizinische Hochschule Hannover = Hannover Medical School
30 Erasmus MC - Erasmus University Medical Center [Rotterdam]
31 University of Sussex
32 University of Brighton
Oliver Pfaar
- Fonction : Auteur
- PersonId : 767433
- ORCID : 0000-0003-4374-9639
Ioana Agache
- Fonction : Auteur
- PersonId : 767614
- ORCID : 0000-0001-7994-364X
Carsten Bindslev-Jensen
- Fonction : Auteur
- PersonId : 786713
- ORCID : 0000-0002-8940-038X
Jean Bousquet
- Fonction : Auteur
- PersonId : 757330
- ORCID : 0000-0002-4061-4766
Philippe Devillier
- Fonction : Auteur
- PersonId : 757986
- ORCID : 0000-0001-6054-1886
Peter Hellings
- Fonction : Auteur
- PersonId : 783928
- ORCID : 0000-0001-6898-688X
Jörg Kleine-Tebbe
- Fonction : Auteur
- PersonId : 791099
- ORCID : 0000-0002-2862-7353
Ludger Klimek
- Fonction : Auteur
- PersonId : 791087
- ORCID : 0000-0002-2455-0192
Marek Jutel
- Fonction : Auteur
- PersonId : 798508
- ORCID : 0000-0003-1555-9379
Antonella Muraro
- Fonction : Auteur
- PersonId : 767935
- ORCID : 0000-0002-5026-5862
Nikolaos Papadopoulos
- Fonction : Auteur
- PersonId : 763391
- ORCID : 0000-0002-4448-3468
Mohamed Shamji
- Fonction : Auteur
- PersonId : 810138
- ORCID : 0000-0003-3425-3463
- IdRef : 260818178
Carmen Vidal
- Fonction : Auteur
- PersonId : 764770
- ORCID : 0000-0002-2844-2754
Stefan Vieths
- Fonction : Auteur
- PersonId : 762613
- ORCID : 0000-0003-3826-6704
Roy Gerth van Wijk
- Fonction : Auteur
- PersonId : 767930
- ORCID : 0000-0002-9608-8742
Résumé
The placebo (Latin "I will please") effect commonly occurs in clinical trials. The psychological and physiological factors associated with patients' expectations about a treatment's positive and negative effects have yet to be well characterized, although a functional prefrontal cortex and intense bidirectional communication between the central nervous system and the immune system appear to be prerequisites for a placebo effect. The use of placebo raises certain ethical issues, especially if patients in a placebo group are denied an effective treatment for a long period of time. The placebo effect appears to be relatively large (up to 77%, relative to pretreatment scores) in controlled clinical trials of allergen immunotherapy (AIT), such as the pivotal, double-blind, placebo-controlled (DBPC) randomized clinical trials currently required by regulatory authorities worldwide. The European Academy of Allergy and Clinical Immunology (EAACI) therefore initiated a Task Force, in order to better understand the placebo effect in AIT and its specific role in comorbidities, blinding issues, adherence, measurement time points, variability and the natural course of the disease. In this Position Paper, the EAACI Task Force highlights several important topics regarding the placebo effect in AIT such as a) regulatory aspects, b) neuroimmunological and psychological mechanisms, c) placebo effect sizes in AIT trials, d) methodological limitations in AIT trial design and e) potential solutions in future AIT trial design. In conclusion, this Position Paper aims to examine the methodological problem of placebo in AIT from different aspects and also to highlight unmet needs and possible solutions for future trials.