• Hugh A Sampson, Wayne G Shreffler, William H Yang, Gordon L Sussman, Terri F Brown-Whitehorn, Kari C Nadeau, Amarjit S Cheema, Stephanie A Leonard, Jacqueline A Pongracic, Christine Sauvage-Delebarre, Amal H Assa'ad, Frederic de Blay, J Andrew Bird, Stephen A Tilles, Franck Boralevi, Thierry Bourrier, Jacques Hébert, Todd D Green, Roy Gerth van Wijk, André C Knulst, Gisèle Kanny, Lynda C Schneider, Marek L Kowalski, and Christophe Dupont.
• Icahn School of Medicine at Mount Sinai, New York, New York.
• JAMA. 2017 Nov 14; 318 (18): 1798-1809.

ImportanceEpicutaneous immunotherapy may have potential for treating peanut allergy but has been assessed only in preclinical and early human trials.ObjectiveTo determine the optimal dose, adverse events (AEs), and efficacy of a peanut patch for peanut allergy treatment.Design, Setting, And ParticipantsPhase 2b double-blind, placebo-controlled, dose-ranging trial of a peanut patch in peanut-allergic patients (6-55 years) from 22 centers, with a 2-year, open-label extension (July 31, 2012-July 31, 2014; extension completed September 29, 2016). Patients (n = 221) had peanut sensitivity and positive double-blind, placebo-controlled food challenges to an eliciting dose of 300 mg or less of peanut protein.InterventionsRandomly assigned patients (1:1:1:1) received an epicutaneous peanut patch containing 50 μg (n = 53), 100 μg (n = 56), or 250 μg (n = 56) of peanut protein or a placebo patch (n = 56). Following daily patch application for 12 months, patients underwent a double-blind, placebo-controlled food challenge to establish changes in eliciting dose.Main Outcomes And MeasuresThe primary efficacy end point was percentage of treatment responders (eliciting dose: ≥10-times increase and/or reaching ≥1000 mg of peanut protein) in each group vs placebo patch after 12 months. Secondary end points included percentage of responders by age strata and treatment-emergent adverse events (TEAEs).ResultsOf 221 patients randomized (median age, 11 years [quartile 1, quartile 3: 8, 16]; 37.6% female), 93.7% completed the trial. A significant absolute difference in response rates was observed at month 12 between the 250-μg (n = 28; 50.0%) and placebo (n = 14; 25.0%) patches (difference, 25.0%; 95% CI, 7.7%-42.3%; P = .01). No significant difference was seen between the placebo patch vs the 100-μg patch. Because of statistical testing hierarchical rules, the 50-μg patch was not compared with placebo. Interaction by age group was only significant for the 250-μg patch (P = .04). In the 6- to 11-year stratum, the response rate difference between the 250-μg (n = 15; 53.6%) and placebo (n = 6; 19.4%) patches was 34.2% (95% CI, 11.1%-57.3%; P = .008); adolescents/adults showed no difference between the 250-μg (n = 13; 46.4%) and placebo (n = 8; 32.0%) patches: 14.4% (95% CI, -11.6% to 40.4%; P = .40). No dose-related serious AEs were observed. The percentage of patients with 1 or more TEAEs (largely local skin reactions) was similar across all groups in year 1: 50-μg patch = 100%, 100-μg patch = 98.2%, 250-μg patch = 100%, and placebo patch = 92.9%. The overall median adherence was 97.6% after 1 year; the dropout rate for treatment-related AEs was 0.9%.Conclusions And RelevanceIn this dose-ranging trial of peanut-allergic patients, the 250-μg peanut patch resulted in significant treatment response vs placebo patch following 12 months of therapy. These findings warrant a phase 3 trial.Trial Registrationclinicaltrials.gov Identifier: NCT01675882.

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