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

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.