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

被引:168
作者
Sampson, Hugh A. [1 ,2 ]
Shreffler, Wayne G. [3 ]
Yang, William H. [4 ]
Sussman, Gordon L. [5 ]
Brown-Whitehorn, Terri F. [6 ]
Nadeau, Kari C. [7 ]
Cheema, Amarjit S. [8 ]
Leonard, Stephanie A. [9 ]
Pongracic, Jacqueline A. [10 ]
Sauvage-Delebarre, Christine [11 ]
Assa'ad, Amal H. [12 ]
de Blay, Frederic [13 ]
Bird, J. Andrew [14 ]
Tilles, Stephen A. [15 ]
Boralevi, Franck [16 ]
Bourrier, Thierry [17 ]
Hebert, Jacques [18 ]
Green, Todd D. [19 ]
van Wijk, Roy Gerth [20 ]
Knulst, Andre C. [21 ]
Kanny, Gisele [22 ]
Schneider, Lynda C. [23 ]
Kowalski, Marek L. [24 ]
Dupont, Christophe [25 ,26 ]
机构
[1] Icahn Sch Med Mt Sinai, New York, NY 10029 USA
[2] DBV Technol, Montrouge, France
[3] Massachusetts Gen Hosp Children, Boston, MA USA
[4] Univ Ottawa, Med Sch, Ottawa, ON, Canada
[5] Univ Toronto, Toronto, ON, Canada
[6] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA
[7] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA
[8] Alpha Med Res, Mississauga, ON, Canada
[9] Univ Calif San Diego, Rady Childrens Hosp, San Diego, CA 92103 USA
[10] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA
[11] Hop St Vincent de Paul, Lille, France
[12] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA
[13] Nouvel Hop Civil, Strasbourg, France
[14] Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA
[15] Northwest Asthma & Allergy Ctr, Seattle, WA USA
[16] Hop Pellegrin Enfants, Bordeaux, France
[17] Nice CHU Lenval, Hop Pediat, Nice, France
[18] CRAAQ, Quebec City, PQ, Canada
[19] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA
[20] Erasmus MC, Rotterdam, Netherlands
[21] Univ Med Ctr, Utrecht, Netherlands
[22] Univ Lorraine, Hop Brabois, Vandoeuvre Les Nancy, France
[23] Boston Childrens Hosp, Boston, MA USA
[24] Med Univ Lodz, Lodz, Poland
[25] Hop Necker Enfants Malad, Paris, France
[26] Univ Paris 05, Paris, France
来源
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION | 2017年 / 318卷 / 18期
关键词
FOOD ALLERGY; DOUBLE-BLIND;
D O I
10.1001/jama.2017.16591
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 300mg or less of peanut protein. INTERVENTIONS Randomly assigned patients (1:1:1:1) received an epicutaneous peanut patch containing 50 mu g (n = 53), 100 mu g (n = 56), or 250 mu g (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 >= 1000mg 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-mu g (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-mu g patch. Because of statistical testing hierarchical rules, the 50-mu g patch was not compared with placebo. Interaction by age group was only significant for the 250-mu g patch (P =.04). In the 6- to 11-year stratum, the response rate difference between the 250-mu g (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-mu g (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-mu g patch = 100%, 100-mu g patch = 98.2%, 250-mu g 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-mu g peanut patch resulted in significant treatment response vs placebo patch following 12 months of therapy. These findings warrant a phase 3 trial.
引用
收藏
页码:1798 / 1809
页数:12
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