Effect of varying doses of epicutaneous immunotherapy vs placebo on reaction to peanut protein exposure among patients with peanut sensitivity: A randomized clinical trial

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. KnulstGisèle Kanny, Lynda C. Schneider, Marek L. Kowalski, Christophe Dupont

Research output: Contribution to journalArticle

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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 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 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-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 RELEVANCE: In 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 REGISTRATION: clinicaltrials.gov Identifier: NCT01675882.

Original languageEnglish (US)
Pages (from-to)1798-1809
Number of pages12
JournalJAMA - Journal of the American Medical Association
Volume318
Issue number18
DOIs
StatePublished - Nov 14 2017

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Immunotherapy
Randomized Controlled Trials
Placebos
Proteins
Peanut Hypersensitivity
Therapeutics
Arachis
Food
Age Groups
Skin

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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, Hugh A.; Shreffler, Wayne G.; Yang, William H.; Sussman, Gordon L.; Brown-Whitehorn, Terri F.; Nadeau, Kari C.; Cheema, Amarjit S.; Leonard, Stephanie A.; Pongracic, Jacqueline A.; Sauvage-Delebarre, Christine; Assa’ad, Amal H.; De Blay, Frederic; Bird, J. Andrew; Tilles, Stephen A.; Boralevi, Franck; Bourrier, Thierry; Hébert, Jacques; Green, Todd D.; Gerth Van Wijk, Roy; Knulst, André C.; Kanny, Gisèle; Schneider, Lynda C.; Kowalski, Marek L.; Dupont, Christophe.

In: JAMA - Journal of the American Medical Association, Vol. 318, No. 18, 14.11.2017, p. 1798-1809.

Research output: Contribution to journalArticle

Sampson, HA, Shreffler, WG, Yang, WH, Sussman, GL, Brown-Whitehorn, TF, Nadeau, KC, Cheema, AS, Leonard, SA, Pongracic, JA, Sauvage-Delebarre, C, Assa’ad, AH, De Blay, F, Bird, JA, Tilles, SA, Boralevi, F, Bourrier, T, Hébert, J, Green, TD, Gerth Van Wijk, R, Knulst, AC, Kanny, G, Schneider, LC, Kowalski, ML & Dupont, C 2017, 'Effect of varying doses of epicutaneous immunotherapy vs placebo on reaction to peanut protein exposure among patients with peanut sensitivity: A randomized clinical trial', JAMA - Journal of the American Medical Association, vol. 318, no. 18, pp. 1798-1809. https://doi.org/10.1001/jama.2017.16591
Sampson, Hugh A. ; Shreffler, Wayne G. ; Yang, William H. ; Sussman, Gordon L. ; Brown-Whitehorn, Terri F. ; Nadeau, Kari C. ; Cheema, Amarjit S. ; Leonard, Stephanie A. ; Pongracic, Jacqueline A. ; Sauvage-Delebarre, Christine ; Assa’ad, Amal H. ; De Blay, Frederic ; Bird, J. Andrew ; Tilles, Stephen A. ; Boralevi, Franck ; Bourrier, Thierry ; Hébert, Jacques ; Green, Todd D. ; Gerth Van Wijk, Roy ; Knulst, André C. ; Kanny, Gisèle ; Schneider, Lynda C. ; Kowalski, Marek L. ; Dupont, Christophe. / Effect of varying doses of epicutaneous immunotherapy vs placebo on reaction to peanut protein exposure among patients with peanut sensitivity : A randomized clinical trial. In: JAMA - Journal of the American Medical Association. 2017 ; Vol. 318, No. 18. pp. 1798-1809.
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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 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 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-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 RELEVANCE: In 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 REGISTRATION: clinicaltrials.gov Identifier: NCT01675882.",
author = "Sampson, {Hugh A.} and Shreffler, {Wayne G.} and Yang, {William H.} and Sussman, {Gordon L.} and Brown-Whitehorn, {Terri F.} and Nadeau, {Kari C.} and Cheema, {Amarjit S.} and Leonard, {Stephanie A.} and Pongracic, {Jacqueline A.} and Christine Sauvage-Delebarre and Assa’ad, {Amal H.} and {De Blay}, Frederic and Bird, {J. Andrew} and Tilles, {Stephen A.} and Franck Boralevi and Thierry Bourrier and Jacques H{\'e}bert and Green, {Todd D.} and {Gerth Van Wijk}, Roy and Knulst, {Andr{\'e} C.} and Gis{\`e}le Kanny and Schneider, {Lynda C.} and Kowalski, {Marek L.} and Christophe Dupont",
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TY - JOUR

T1 - Effect of varying doses of epicutaneous immunotherapy vs placebo on reaction to peanut protein exposure among patients with peanut sensitivity

T2 - A randomized clinical trial

AU - Sampson, Hugh A.

AU - Shreffler, Wayne G.

AU - Yang, William H.

AU - Sussman, Gordon L.

AU - Brown-Whitehorn, Terri F.

AU - Nadeau, Kari C.

AU - Cheema, Amarjit S.

AU - Leonard, Stephanie A.

AU - Pongracic, Jacqueline A.

AU - Sauvage-Delebarre, Christine

AU - Assa’ad, Amal H.

AU - De Blay, Frederic

AU - Bird, J. Andrew

AU - Tilles, Stephen A.

AU - Boralevi, Franck

AU - Bourrier, Thierry

AU - Hébert, Jacques

AU - Green, Todd D.

AU - Gerth Van Wijk, Roy

AU - Knulst, André C.

AU - Kanny, Gisèle

AU - Schneider, Lynda C.

AU - Kowalski, Marek L.

AU - Dupont, Christophe

PY - 2017/11/14

Y1 - 2017/11/14

N2 - 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 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 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-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 RELEVANCE: In 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 REGISTRATION: clinicaltrials.gov Identifier: NCT01675882.

AB - 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 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 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-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 RELEVANCE: In 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 REGISTRATION: clinicaltrials.gov Identifier: NCT01675882.

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