Effect of Varying Doses of Epicutaneous Immunotherapy Versus Placebo on Reaction to Peanut Protein Exposure Among Patients With Peanut Sensitivity: A Randomized Clinical Trial

PURPOSE OF THE STUDY. To determine the optimal dose, adverse events, and efficacy of an epicutaneous patch for the treatment of peanut allergy. STUDY POPULATION. The study included 221 patients with peanut allergy aged 6 to 55 years from 22 centers. Peanut allergy was defined as a history of reaction with positive skin prick test results, serum-specific immunoglobulin E, and double-blind, placebo-controlled (DBPC) food challenge. METHODS. This was a phase 2b DBPC, dose-ranging study of peanut epicutaneous immunotherapy. Patients were randomly assigned to 50-μg, 100-μg, 250-μg, or placebo-daily patches for 12 months with a subsequent 2-year open-label extension. During the extension, patients initially receiving the placebo were started on active treatment. Patients underwent DBPC food challenges at 12, 24, and 36 months. The primary end point was the percentage of treatment responders defined as a ≥10-fold increase in eliciting dose and/or tolerating 1000 mg of peanut protein in each group versus the placebo at 12 months. Secondary end points included the percentage of responders by age, treatment-emergent adverse events, and rates of treatment discontinuation. RESULTS. There was a significant response to the 250-μg patch compared with the placebo at 12 months (P = .01). There was no significant difference detected at lower doses. The response rate for the 250-μg patch versus the placebo was only significant for the 6- to 11-year age group (P = .008), whereas the adolescent adult group had no significant difference (P = .4). Adverse events were primarily local skin reactions and were not dose dependent. A total 6.3% of participants discontinued the study prematurely. CONCLUSIONS. The 250-μg epicutaneous peanut immunotherapy provided significant treatment response versus the placebo after 12 months with no serious adverse events related to the patch. Further study of this therapy is warranted. REVIEWER COMMENTS. Peanut allergy affects ∼2% of children in the United States, and there is currently no US Food and Drug Administration–approved proactive treatment to alleviate the burden of disease and mitigate the risk of reactions. This phase 2b study reveals the safety and efficacy of an epicutaneous treatment of peanut allergy. Additional analyses in the supplement suggest that higher rates of efficacy are seen with longer duration of treatment, which is similar to other routes of immunotherapy. Notably, a high rate of sustained unresponsiveness appears to be