AUTHOR=Braun Camille , Azzano Pauline , Gingras-Lessard Florence , Roy Émilie , Samaan Kathryn , Graham François , Paradis Louis , Des Roches Anne , Bégin Philippe 

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

JOURNAL=Frontiers in Medicine

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1198173

DOI=10.3389/fmed.2023.1198173

ISSN=2296-858X

ABSTRACT=Context. While oral immunotherapy (OIT) has been shown to promote 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 disease. 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 adjuvant to allergen immunotherapy. The goal of this study is to explore the potential efficacy of abatacept at promoting immune tolerance to food allergens during OIT in humans.
Methods. In 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 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.
Discussion. This is the first study assessing the use of abatacept as an adjuvant to allergen immunotherapy in human. The ability of abatacept to modulate the peanut-specific immune response during OIT, as observed in preclinical studies, 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.