Abatacept to induce remission of peanut allergy during oral immunotherapy (ATARI): protocol for a phase 2a randomized controlled trial

Frontiers in Medicine

Medicine

Pauline Azzano¹  Florence Gingras-Lessard²  Émilie Roy²  Anne Des Roches²  Kathryn Samaan²  Philippe Bégin³  Louis Paradis³  François Graham³  Camille Braun⁴ 

[1] Department of Pediatric Hepatogastroenterology and Nutrition, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France;Department of Pediatrics, Section of Allergy and Clinical Immunology, Centre Hospitalier Universitaire Sainte-Justine, Montreal, QC, Canada;Department of Pediatrics, Section of Allergy and Clinical Immunology, Centre Hospitalier Universitaire Sainte-Justine, Montreal, QC, Canada;Department of Medicine, Section of Allergy and Clinical Immunology, Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada;Department of Pediatrics, Section of Allergy and Clinical Immunology, Centre Hospitalier Universitaire Sainte-Justine, Montreal, QC, Canada;Department of Pediatrics, Pneumology, Allergy, Cystic Fibrosis, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France;Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR 5308, Université Lyon 1, ENS de Lyon, Lyon, France;

关键词: food allergy;    oral immunotherapy (OIT);    sustained unresponsiveness;    abatacept;    CTLA-4;    peanut allergy;    desensitization;   

DOI  :  10.3389/fmed.2023.1198173

 received in 2023-03-31, accepted in 2023-06-06,  发布年份 2023

来源: Frontiers

【 摘 要 】

ContextWhile oral immunotherapy (OIT) has been shown to promote the remission of mild peanut allergy in young children, there is still an unmet need for a disease-modifying intervention for older patients and those with severe diseases. In mice models, abatacept, a cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) immunoglobulin fusion protein, has been shown to promote immune tolerance to food when used as an adjuvant to allergen immunotherapy. The goal of this study is to explore the potential efficacy of abatacept in promoting immune tolerance to food allergens during OIT in humans.MethodsIn this phase 2a proof-of-concept study (NCT04872218), 14 peanut-allergic participants aged from 14 to 55 years will be randomized at a 1:1 ratio to abatacept vs. placebo for the first 24 weeks of a peanut OIT treatment (target maintenance dose of 300 mg peanut protein). The primary outcome will be the suppression of the OIT-induced surge in peanut-specific IgE/total IgE at 24 weeks, relative to the baseline. Sustained unresponsiveness will be assessed as a secondary outcome starting at 36 weeks by observing incremental periods of peanut avoidance followed by oral food challenges.DiscussionThis is the first study assessing the use of abatacept as an adjuvant to allergen immunotherapy in humans. As observed in preclinical studies, the ability of abatacept to modulate the peanut-specific immune response during OIT will serve as a proxy outcome for the development of clinical tolerance, given the small sample size. The study will also test a new patient-oriented approach to sustained tolerance testing in randomized controlled trials.

【 授权许可】

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Copyright © 2023 Braun, Azzano, Gingras-Lessard, Roy, Samaan, Graham, Paradis, Des Roches and Bégin.