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,Hugh A. Sampson,Wayne G. Shreffler,William H. Yang,Gordon Sussman,Terri F. Brown-Whitehorn,Kari C. Nadeau,Amarjit Cheema,Stephanie A. Leonard,Jacqueline A. Pongracic,Christine Sauvage-Delebarre,Amal Assa'ad,Frédéric 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,Christophe Dupont,Christophe Dupont +25 more
TLDR
A dose-ranging trial of a peanut patch in peanut-allergic patients and a double-blind, placebo-controlled food challenge to establish changes in eliciting dose to determine the optimal dose, adverse events (AEs), and efficacy of aanut patch for peanut allergy treatment.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.read more
Citations
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Journal ArticleDOI
Food allergy: A review and update on epidemiology, pathogenesis, diagnosis, prevention, and management.
TL;DR: This review provides general information to serve as a primer for those embarking on understanding food allergy and also details advances and updates in epidemiology, pathogenesis, diagnosis, and treatment that have occurred over the 4 years since the last comprehensive review.
Journal ArticleDOI
Effect of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Ingestion among Children with Peanut Allergy: The PEPITES Randomized Clinical Trial
David Fleischer,Matthew Greenhawt,Gordon Sussman,Philippe Bégin,Anna Nowak-Wegrzyn,Daniel Petroni,Kirsten Beyer,Terri F. Brown-Whitehorn,Jacques Hébert,Jonathan O'b Hourihane,Dianne E. Campbell,Stephanie A. Leonard,R. Sharon Chinthrajah,Jacqueline A. Pongracic,Stacie M. Jones,Lars Lange,Hey Chong,Todd D. Green,Todd D. Green,Robert J. Wood,Amarjit Cheema,Susan L. Prescott,Pete Smith,William H. Yang,Edmond S. Chan,Aideen Byrne,Amal Assa'ad,J. Andrew Bird,Edwin H. Kim,Lynda C. Schneider,Carla M. Davis,Bruce J. Lanser,Romain Lambert,Wayne G. Shreffler +33 more
TL;DR: Among peanut-allergic children aged 4 to 11 years, the percentage difference in responders at 12 months with the 250-&mgr;g peanut-patch therapy vs placebo was 21.7% and was statistically significant, but did not meet the prespecified lower bound of the confidence interval criterion for a positive trial result.
Journal ArticleDOI
IgE-Mediated Food Allergy
TL;DR: Management of food allergies requires strict avoidance measures, counseling of the family about constant vigilance, and prompt treatment of allergic reactions with emergency medications, and future treatments for IgE-mediated food allergy evaluated in clinical trials include epicutaneous, sublingual, and oral immunotherapy.
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Microneedles for painless transdermal immunotherapeutic applications
Hamed Amani,Mohammad-Ali Shahbazi,Mohammad-Ali Shahbazi,Carmine D'Amico,Flavia Fontana,Samin Abbaszadeh,Hélder A. Santos +6 more
TL;DR: Microneedles possess many outstanding properties, such as the ability for the painless traverse of the stratum corneum, minimal invasiveness, facile fabrication, excellent biocompatibility, convenient administration, and bypassing first-pass metabolism that allows direct translocation of therapeutics into the systematic circulation.
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Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care
Heimo Breiteneder,Zuzana Diamant,Zuzana Diamant,Thomas Eiwegger,Wytske Fokkens,Claudia Traidl-Hoffmann,Kari C. Nadeau,Robyn E O'Hehir,Liam O'Mahony,Oliver Pfaar,María José Torres,De Yun Wang,Luo Zhang,Cezmi A. Akdis +13 more
TL;DR: Recent developments in research and patient care and future trends in the discipline are reviewed and topics on food allergy, biologics, small molecules, and novel therapeutic concepts in allergen‐specific immunotherapy for airway disease are highlighted.
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