Dose-related Allergic Reactions Decrease over Time During Peanut Oral Immunotherapy in a Large, Randomized, Double-blind, Placebo-controlled, Phase 2 Study

Oral immunotherapy (OIT) is currently under investigation for the treatment of peanut allergy and long-term safety is unknown. We evaluated OIT-related adverse events (AEs) during multi-year peanut OIT to better understand the long-term safety of OIT. 120 participants aged 7-55 years with confirmed peanut allergy were enrolled in a double-blind, placebo-controlled, phase 2 study of peanut OIT. Participants were randomized to escalate to and maintain 4000 mg peanut protein (n=95) or placebo (n=25) daily over 104 weeks. The per-person AE rate was calculated by dividing the number of AEs per year by the number of doses taken each year. Differences in per-person median AE rates between groups of interest were evaluated using Kruskal-Wallis rank sum test. The overall AE rate significantly decreased from 0.50 in year 1 to 0.14 in year 2 (p<0.0001), with a significantly greater reduction in AE rates from year 1 to year 2 in the peanut arm compared to placebo (-0.22 vs 0.00, p=0.0043). The rate of moderately severe AEs significantly declined from year 1 to year 2 in the peanut arm (0.09 vs 0.00, p=0.093). Participants reporting AEs related to accidental peanut ingestion decreased between year 1 (9%) and 2 (2%) in the peanut arm, while placebo did not change (12% to 16%). Participants requiring the use of epinephrine declined within the peanut arms with longer duration on peanut (19% year 1, 13% year 2). These findings show that the safety profile of peanut OIT improves as time on therapy increases.