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JAMA. 2017 Nov 14;318(18):1798-1809. doi: 10.1001/jama.2017.16591.

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

Author information

1
Icahn School of Medicine at Mount Sinai, New York, New York.
2
DBV Technologies, Montrouge, France.
3
Massachusetts General Hospital for Children, Boston.
4
University of Ottawa Medical School, Ottawa, Ontario, Canada.
5
University of Toronto, Toronto, Ontario, Canada.
6
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
7
Stanford University School Medicine, Palo Alto, California.
8
Alpha Medical Research, Mississauga, Ontario, Canada.
9
Rady Children's Hospital, University of California, San Diego.
10
Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.
11
Hôpital Saint Vincent de Paul, Lille, France.
12
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
13
Nouvel Hôpital Civil, Strasbourg, France.
14
University of Texas Southwestern Medical Center, Dallas.
15
Northwest Asthma and Allergy Center, Seattle, Washington.
16
Hôpital Pellegrin-Enfants, Bordeaux, France.
17
Hôpitaux Pédiatriques de Nice CHU-Lenval, Nice, France.
18
CRAAQ, Québec, Canada.
19
Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
20
Erasmus Medical Center, Rotterdam, the Netherlands.
21
University Medical Center, Utrecht, the Netherlands.
22
Hôpitaux de Brabois, University of Lorraine, Vandœuvre-lès-Nancy, France.
23
Boston Children's Hospital, Boston, Massachusetts.
24
Medical University of Lodz, Lodz, Poland.
25
Hôpital Necker, Enfants Malades, Paris, France.
26
Université Paris-Descartes, Paris, France.

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.

PMID:
29136445
PMCID:
PMC5820709
DOI:
10.1001/jama.2017.16591
[Indexed for MEDLINE]
Free PMC Article

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