Effect of Epicutaneous Immunotherapy Versus Placebo on Reaction to Peanut Protein Ingestion Among Children With Peanut Allergy: The PEPITES Randomized Clinical Trial

Abstract

To assess the efficacy and adverse events of epicutaneous immunotherapy with a peanut patch among children with peanut allergy.The study included 356 children with peanut allergy aged 4 to 11 years without a history of severe peanut-related anaphylaxis who showed objective signs and symptoms of reactivity at an eliciting dose of ≤300 mg of peanut protein during a double-blinded, placebo-controlled food challenge.This study was a phase 3, randomized, double-blinded, placebo-controlled multicenter trial. Study participants were stratified into low- (≤10 mg) and high-eliciting dose (10–300 mg) subgroups on the basis of participants’ screening eliciting dose. Participants were then randomly assigned into groups receiving a daily epicutaneous patch containing 250 µg of peanut protein (n = 238) or a daily placebo patch (n = 118). Treatment response was defined as a posttreatment eliciting dose of ≥300 or ≥1000 mg of peanut protein for the pretreatment low- and high-eliciting dose subgroups, respectively. The treatment effect of the immunotherapy was determined by the response rate difference between the treatment and placebo groups after 12 months. A margin of 15% was selected as the lower bound of the 95% confidence interval (CI) for determining a positive trial result. The incidence of treatment-emergent adverse events (TEAEs) was also followed in each group.After 12 months, the response rates of the treatment (35.3%) and placebo (13.6%) groups were compared, showing a difference of 21.7% that was statistically significant (P < .001). However, the resulting lower bound of the 95% CI was 12.4%, which did not achieve the pretrial 15% criterion for clinically relevant significance. The incidence of TEAEs was 95.4% in the treatment group and 89% in the placebo group, in which application site reactions were the most common TEAE observed in both groups. There were 4 TEAEs in 3 treatment group participants that were classified as moderate anaphylactic reactions, all cases were appropriately treated, and 2 of these participants permanently discontinued the study.This study demonstrated a statistically significant difference between response rates of the peanut patch and placebo patch groups on the basis of eliciting doses during food challenges before and after the 12-month trial period. The results could not be considered a positive trial because the lower bound of the 95% CI was not met.Epicutaneous immunotherapy stands as a candidate for therapy for children with peanut allergy who would benefit from desensitization and lower risk of potentially life-threatening anaphylaxis resulting from accidental peanut exposure. Given sparse historical data for the assessment of food allergy immunotherapy trials, the lower bound criterion for the 95% CI in this study was set at 15% under US Food and Drug Administration guidance but is considered by some to be arbitrary in nature. The failure of this study’s results to meet this preset criterion signifies the results may not be clinically significant, despite showing a statistically significant difference in response rate between the treatment and placebo groups. Nevertheless, this treatment option may offer some clinical benefit to a vulnerable population, but this should be weighed on the generally low incidence of severe reactions in light of appropriate food avoidance. A longer trial, beyond the 12-month duration of this study, may prove to show clinically relevant results and may offer further insight into the maintenance of desensitization.