Efficacy and Safety of Abatacept Versus Placebo During Peanut Oral Immunotherapy for Adults With Severe Peanut Allergy

Abstract

Background Unmet needs remain for disease‐modifying interventions for the treatment of severe persistent food allergies. In mice models, abatacept, a cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4) immunoglobulin fusion protein, promotes immune tolerance to food proteins, and suppresses the initial allergen‐related induction of specific immunoglobulin E (IgE) when used as an adjuvant to allergen immunotherapy. Methods In this Phase 2a placebo‐controlled clinical trial, 14 peanut‐allergic participants (14–50 years old) with specific IgE > 50 kU/L were randomized 1:1 to adjuvant abatacept vs. placebo to peanut oral immunotherapy (OIT) for 24 weeks, followed by 12 weeks of OIT alone. With the hypothesis that abatacept suppresses the transient OIT‐induced increase in specific IgE, the primary outcome was the relative change from baseline of the peanut‐specific/total IgE ratio at 24 weeks. Sustained unresponsiveness was assessed as a secondary outcome with repeated oral food challenges (OFCs) following incremental periods of peanut avoidance. Results No significant difference in the relative change in peanut‐specific/total IgE ratio from baseline was observed between groups (placebo group 87.9% vs. abatacept group 48.2%, p ‐value 0.26). Median minimal reactive doses on repeated OFCs were similar in both groups (3000 mg) after 4 weeks of peanut avoidance. Lower adverse event rates including anaphylaxis were observed in the abatacept group (5.9 vs. 10 per participant, p ‐value 0.006). Conclusion Compared to placebo, abatacept did not suppress the allergen‐related induction of peanut‐specific IgE relative to their total at 24 weeks, but improved OIT tolerability in this severely allergic adult population. Independently of abatacept, most participants achieved sustained unresponsiveness with OIT.