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

Sampson, H. A.; Shreffler, W. G.; Yang, W. H.; Sussman, G. L.; Brown-Whitehorn, T. F.; Nadeau, K. C.; Cheema, A. S.; Leonard, S. A.; Pongracic, J. A.; Sauvage-Delebarre, C.; Assa'ad, A. H.; de Blay, F.; Bird, J. A.; Tilles, S. A.; Boralevi, F.; Bourrier, T.; Hebert, J.; Green, T. D.; Gerth van Wijk, R.; Knulst, A. C.; Kanny, G.; Schneider, L. C.; Kowalski, M. L.; Dupont, C.

JAMA. 2017 Nov 15; 318(18):1798-1809

Abstract

Importance: Epicutaneous immunotherapy may have potential for treating peanut allergy but has been assessed only in preclinical and early human trials. Objective: To determine the optimal dose, adverse events (AEs), and efficacy of a peanut patch for peanut allergy treatment. Design, Setting, and Participants: Phase 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. Interventions: Randomly assigned patients (1:1:1:1) received an epicutaneous peanut patch containing 50 mug (n = 53), 100 mug (n = 56), or 250 mug (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 Measures: The 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). Results: Of 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-mug (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-mug patch. Because of statistical testing hierarchical rules, the 50-mug patch was not compared with placebo. Interaction by age group was only significant for the 250-mug patch (P = .04). In the 6- to 11-year stratum, the response rate difference between the 250-mug (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-mug (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-mug patch = 100%, 100-mug patch = 98.2%, 250-mug 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 Relevance: In this dose-ranging trial of peanut-allergic patients, the 250-mug peanut patch resulted in significant treatment response vs placebo patch following 12 months of therapy. These findings warrant a phase 3 trial. Trial Registration: clinicaltrials.gov Identifier: NCT01675882.

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