Sustained outcomes in oral immunotherapy for peanut allergy (POISED study): a large, randomised, double-blind, placebo-controlled, phase 2 study

Abstract

Dietary avoidance is currently recommended for peanut allergies. We evaluated sustained effects of treating peanut allergy with oral immunotherapy (OIT) in the first phase 2 randomized-controlled long-term study in adults and children. In a double-blind, placebo-controlled, randomized study, 120 peanut-allergic participants (7-53 years old) received up to 4 g of peanut protein or placebo daily for 3 years. Participants received placebo (N=25) or peanut protein (N=95) over 104 weeks; 60 then discontinued (peanut-0) while 35 received 300 mg daily (peanut-300). Double-blind, placebo-controlled food challenges (DBPCFCs) to 4 g peanut protein were conducted at baseline, week 104, and every 13 weeks thereafter for one year. The primary endpoint was reached at week 117 after 3 months of discontinuation (testing sustained unresponsiveness): 21/60 (35%) peanut-0 participants passed the challenge with no reaction versus 1/25 (4%) placebo (primary endpoint, P=0.002). Time to failure was significantly longer in peanut-300 vs. peanut-0 vs. placebo arms (P<0.0001). The percentage of participants passing DBPCFCs in peanut-300 declined significantly (weeks 104 vs. 156; 83% vs. 37%, P<0.001). Adverse allergic reactions decreased over time in all arms. Peanut-specific IgG4/IgE levels were higher (P<0.001), and Ara h 2-specific IgE (P<0.001) and basophil activation responses (P=0.037) were lower, at baseline in those achieving sustained unresponsiveness at week 117. Peanut OIT desensitizes most peanut-allergic individuals to 4 g peanut protein but discontinuation, or even a reduction to 300 mg daily, increases the likelihood of regaining clinical reactivity to peanut. Baseline blood tests correlate with week 117 treatment outcomes.