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

Purpose Of The Study: To assess the efficacy and adverse events of epicutaneous immunotherapy with a peanut patch among children with peanut allergy. Study Population: 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. Methods: 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. Results: 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. Conclusions: 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.