An evaluation of factors influencing response to epicutaneous immunotherapy for peanut allergy in the PEPITES trial.

BACKGROUND Epicutaneous immunotherapy (EPIT) for peanut allergy is a potential novel immunotherapy that utilizes the unique cutaneous immunologic properties to induce desensitization. A randomized, double-blind, placebo-controlled Phase 3 trial (PEPITES) in peanut-allergic children 4-11 years demonstrated an epicutaneous patch (DBV712) with 250 micrograms peanut protein was statistically superior to placebo in inducing desensitization following 12 months of daily treatment. OBJECTIVE To investigate what baseline and in-study factors influenced response to DBV712 250 micrograms, with a focus on patch adhesion, by posthoc analysis of PEPITES data. METHODS A posthoc multivariate model built with log-transformed Month 12 eliciting dose (ED) as the dependent variable was used to assess the influence of baseline characteristics and patch adhesion. Baseline characteristics and treatment responsewere also evaluated by stratifying subjects into decile subgroups by patch detachment rates over the 12-month study. RESULTS Multivariate analysis identified higher baseline ED and lower baseline peanut-specific IgE as the variables mostpredictive of higher Month 12 ED, followed by mean daily patch application duration, baseline SCORing Atopic Dermatitis(SCORAD) score, and age. By decile stratification, no association between patch detachment and treatment response wasidentified for 80% of DBV712-treated subjects. All DBV712-treated subjects, including those with the highest patch detachment rates, demonstrated treatment benefit measured by fold-changes in geometric mean ED. CONCLUSION We identified subject baseline characteristics of higher baseline ED and lower baseline peanut-specific IgE asmost predictive of higher Month 12 ED. For the majority of treated subjects, patch detachment did not impact treatmentresponse. A minority of subjects, highly sensitive to peanut at baseline, had lower prespecified responder rates and higherpatch detachment rates, yet still benefited from treatment based upon fold-changes in ED.