Placebo effects in allergen immunotherapy—An EAACI Task Force Position Paper

Pfaar, Oliver; Agache, Ioana; Bergmann, Karl‐Christian; Bindslev‐Jensen, Carsten; Bousquet, Jean; Creticos, Peter S.; Devillier, Philippe; Durham, Stephen R.; Hellings, Peter; Kaul, Susanne; Kleine‐Tebbe, Jörg; Klimek, Ludger; Jacobsen, Lars; Jutel, Marek; Muraro, Antonella; Papadopoulos, Nikolaos G.; Rief, Winfried; Scadding, Glenis; Schedlowski, Manfred; Shamji, Mohamed H.; Sturm, Gunter J.; Ree, Ronald van; Vidal, Carmen; Vieths, Stefan; Wedi, Bettina; Wijk, Roy Gerth van; Frew, Anthony J.

doi:10.1111/all.14331

Cited by 40 publications

(61 citation statements)

References 129 publications

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“… 47 The placebo effect in DBPC trials using AECs ranged from +11% to +0,5% after 6 months using the TNSS (−7% after 4 months in 1 trial), and −4% to −17% after 6 months using the Total Ocular Symptom Score in house dust mite (HDM) allergic patients with sublingual immunotherapy (SLIT), and was −18.5% in grass SLIT (Rhinoconjunctivitis Total Symptom Score after 4 months) and −18.8% in birch subcutaneous immunotherapy (SCIT) (TSS after 10 weeks). 48 The efficacy of the symbiotic product in our study exceeded these previously reported effects of placebo groups in AEC trials with a reduction in the median TNSS of 50% and median TSS of 80%. So, even without being able to control for placebo effects in this study, we are confident that the symbiotic product shows clinically relevant improvement for patients with allergic rhinitis.…”

Section: Discussionsupporting

confidence: 52%

First evaluation of a symbiotic food supplement in an allergen exposure chamber in birch pollen allergic patients

Bergmann

Krause

Hiller³

et al. 2021

World Allergy Organization Journal

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Background Allergic rhinitis/rhinoconjunctivitis is the most common immune disease worldwide, but still largely underestimated, underdiagnosed, and undertreated. Dysbiosis and reduced microbial diversity is linked to the development of allergies, and the immunomodulatory effects of pro- and prebiotics might be used to counteract microbiome dysbiosis in allergy. Adequate symbiotic (multi-strain pro-, plus prebiotic) supplementation can be suggested as a complementary approach in the management of allergic rhinitis. Objective The effects of the daily intake of a symbiotic food supplement (combination of Lactobacillus acidophilus NCFM and Bifidobacterium lactis BL-04 with Fructo-Oligosaccharides) for 4 months in birch pollen allergic rhinoconjunctivitis patients were investigated for the first time in an allergen exposure chamber (AEC) allowing standardised, reproducible pollen exposure before and after intake. Methods Eligible patients were exposed to birch pollen (8000 pollen/m³ for 120 min) at the GA 2 LEN AEC, at baseline (V1) and final visit (V3) outside the season. The Total Symptom Score (TSS) and the scores for nose, eye, bronchial system, and others were evaluated every 10 min during exposure. Other secondary endpoints were the changes in well-being, Peak Nasal Inspiratory Flow (PNIF), lung function parameters, and safety. Co-primary endpoints were differences in Total Nasal Symptom Score (TNSS) and TSS after 120 min of exposure between both visits. Temporal evolution of symptom scores were analysed in an exploratory way using linear mixed effects models. Results 27 patients (mean age 45 years, 15% male) completed the study. Both co-primary endpoints showed significant improvement after intake of the symbiotic. Median TNSS and TSS were decreased 50% and 80% at 120 min (adjusted p-value = 0.025 and p < 0.01 respectively). All four symptom scores and the personal well-being, improved to a clinically relevant extent over time, visible by a weaker increase in symptoms during 120 min of the final birch pollen exposure. No relevant differences were observed for PNIF, PEF, and spirometry. There were no airway obstructions or lung restrictions before and after both exposures. Late phase reactions after exposure were reduced after V3, documenting a better birch pollen tolerability of the patients. The safety and tolerability profile of the symbiotic food supplement was excellent, no adverse events (AEs) were observed. Conclusions This first evaluation of a symbiotic food supplement in an AEC in rhinoconjunctivitis patients with or without asthma induced by birch pollen revealed a significant beneficial effect, harnessing significant improvements of symptoms and well-being while maintaining an excellent safety and tolerability profile.

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Section: Discussionsupporting

confidence: 52%

First evaluation of a symbiotic food supplement in an allergen exposure chamber in birch pollen allergic patients

Bergmann

Krause

Hiller³

et al. 2021

World Allergy Organization Journal

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“…348,349 Recently, the EAACI has published a Position Paper reporting the impact of the placebo effect in AIT from different methodological perspectives and outlining possible strategies to minimize this bias in clinical trials. 350 Taken together, further emphasis should be put on international collaborations of clinical experts, methodologists and regulatory authorities to optimize methodological standards for AIT clinical development programs aimed to increase the level of evidence of AIT as the only disease-modifying therapy available. 334,337,351…”

Section: B I Omark Er S Of the Epithelial Barriermentioning

confidence: 99%

Biomarkers for diagnosis and prediction of therapy responses in allergic diseases and asthma

Breiteneder

Peng

Agache

et al. 2020

Allergy

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“…One researcher (IK) use the terms "placebo/nocebo response" and "placebo/nocebo effect" in the opposite way [5]. In a recent position paper from the European Academy of Allergy and Clinical Immunology, the term "placebo effect" was defined as "the psychological and physiological benefits of seeking advice and receiving treatment for a medical problem, independently of the prescribed treatment's pharmacological effects per se" [6]. Historical and traditional reasons may explain the differences.…”

Section: The Effect -Response Controversymentioning

confidence: 99%

European Headache Federation recommendations for placebo and nocebo terminology

et al. 2020

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Background and aim Despite recent publications, practitioners remain unfamiliar with the current terminology related to the placebo and nocebo phenomena observed in clinical trials and practice, nor with the factors that modulate them. To cover the gap, the European Headache Federation appointed a panel of experts to clarify the terms associated with the use of placebo in clinical trials. Methods The working group identified relevant questions and agreed upon recommendations. Because no data were required to answer the questions, the GRADE approach was not applicable, and thus only expert opinion was provided according to an amended Delphi method. The initial 12 topics for discussion were revised in the opinion of the majority of the panelists, and after a total of 6 rounds of negotiations, the final agreement is presented. Results/recommendations Two primary and mechanism-based recommendations are provided for the results of clinical trials: [1] to distinguish the placebo or nocebo response from the placebo or nocebo effect; and [2] for any favorable outcome observed after placebo administration, the term “placebo response” should be used, and for any unfavorable outcome recorded after placebo administration, the term “nocebo response” should be used (12 out of 17 panelists agreed, 70.6% agreement). The placebo or nocebo responses are attributed to a set of factors including those that are related to the medical condition (e.g. natural history, random comorbidities, etc.), along with idiosyncratic ones, in which the placebo or nocebo effects are attributed to idiosyncratic, or nonspecific mechanisms, exclusively (e.g. expectation, conditioning, observational learning etc.). To help investigators and practitioners, the panel summarized a list of environmental factors and idiosyncratic dynamics modulating placebo and nocebo effects. Some of them are modifiable, and investigators or physicians need to know about them in order to modify these factors appropriately to improve treatment. One secondary recommendation addresses the use of the terms “placebo” and “nocebo” (“placebos” and “nocebos” in plural), which refer to the triggers of the placebo/nocebo effects or responses, respectively, and which are inert agents or interventions that should not be confused with the placebo/nocebo responses or effects themselves (all panelists agreed, 100% agreement). Conclusion The working group recommends distinguishing the term response from effect to describe health changes from before to after placebo application and to distinguish the terms placebo(s) or nocebo(s) from the health consequences that they cause (placebo/nocebo responses or effects).

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Placebo effects in allergen immunotherapy—An EAACI Task Force Position Paper

Cited by 40 publications

References 129 publications

First evaluation of a symbiotic food supplement in an allergen exposure chamber in birch pollen allergic patients

First evaluation of a symbiotic food supplement in an allergen exposure chamber in birch pollen allergic patients

Biomarkers for diagnosis and prediction of therapy responses in allergic diseases and asthma

European Headache Federation recommendations for placebo and nocebo terminology

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