PMID- 29136445 OWN - NLM STAT- MEDLINE DCOM- 20171127 LR - 20220330 IS - 1538-3598 (Electronic) IS - 0098-7484 (Print) IS - 0098-7484 (Linking) VI - 318 IP - 18 DP - 2017 Nov 14 TI - Effect of Varying Doses of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Exposure Among Patients With Peanut Sensitivity: A Randomized Clinical Trial. PG - 1798-1809 LID - 10.1001/jama.2017.16591 [doi] 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 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. FAU - Sampson, Hugh A AU - Sampson HA AD - Icahn School of Medicine at Mount Sinai, New York, New York. AD - DBV Technologies, Montrouge, France. FAU - Shreffler, Wayne G AU - Shreffler WG AD - Massachusetts General Hospital for Children, Boston. FAU - Yang, William H AU - Yang WH AD - University of Ottawa Medical School, Ottawa, Ontario, Canada. FAU - Sussman, Gordon L AU - Sussman GL AD - University of Toronto, Toronto, Ontario, Canada. FAU - Brown-Whitehorn, Terri F AU - Brown-Whitehorn TF AD - Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. FAU - Nadeau, Kari C AU - Nadeau KC AD - Stanford University School Medicine, Palo Alto, California. FAU - Cheema, Amarjit S AU - Cheema AS AD - Alpha Medical Research, Mississauga, Ontario, Canada. FAU - Leonard, Stephanie A AU - Leonard SA AD - Rady Children's Hospital, University of California, San Diego. FAU - Pongracic, Jacqueline A AU - Pongracic JA AD - Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois. FAU - Sauvage-Delebarre, Christine AU - Sauvage-Delebarre C AD - Hopital Saint Vincent de Paul, Lille, France. FAU - Assa'ad, Amal H AU - Assa'ad AH AD - Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. FAU - de Blay, Frederic AU - de Blay F AD - Nouvel Hopital Civil, Strasbourg, France. FAU - Bird, J Andrew AU - Bird JA AD - University of Texas Southwestern Medical Center, Dallas. FAU - Tilles, Stephen A AU - Tilles SA AD - Northwest Asthma and Allergy Center, Seattle, Washington. FAU - Boralevi, Franck AU - Boralevi F AD - Hopital Pellegrin-Enfants, Bordeaux, France. FAU - Bourrier, Thierry AU - Bourrier T AD - Hopitaux Pediatriques de Nice CHU-Lenval, Nice, France. FAU - Hebert, Jacques AU - Hebert J AD - CRAAQ, Quebec, Canada. FAU - Green, Todd D AU - Green TD AD - Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. FAU - Gerth van Wijk, Roy AU - Gerth van Wijk R AD - Erasmus Medical Center, Rotterdam, the Netherlands. FAU - Knulst, Andre C AU - Knulst AC AD - University Medical Center, Utrecht, the Netherlands. FAU - Kanny, Gisele AU - Kanny G AD - Hopitaux de Brabois, University of Lorraine, Vandoeuvre-les-Nancy, France. FAU - Schneider, Lynda C AU - Schneider LC AD - Boston Children's Hospital, Boston, Massachusetts. FAU - Kowalski, Marek L AU - Kowalski ML AD - Medical University of Lodz, Lodz, Poland. FAU - Dupont, Christophe AU - Dupont C AD - Hopital Necker, Enfants Malades, Paris, France. AD - Universite Paris-Descartes, Paris, France. LA - eng SI - ClinicalTrials.gov/NCT01675882 SI - ClinicalTrials.gov/NCT01675882 PT - Clinical Trial, Phase II PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA JT - JAMA JID - 7501160 RN - 0 (Allergens) SB - IM MH - Administration, Cutaneous MH - Adolescent MH - Adult MH - Allergens/*administration & dosage MH - Arachis/*immunology MH - Child MH - Desensitization, Immunologic/*methods MH - Dose-Response Relationship, Immunologic MH - Double-Blind Method MH - Female MH - Humans MH - Male MH - Middle Aged MH - Peanut Hypersensitivity/*therapy PMC - PMC5820709 COIS- Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Sampson reports being a part-time employee of DBV Technologies; receiving consultant fees from Allertein Therapeutics, UCB, and Hycor and personal fees from UpToDate; holding stock options in DBV Technologies and Allertein Therapeutics; receiving grants from the National Institutes of Health, National Institute of Allergy and Infectious Diseases, and Food Allergy Research & Education; and co-owning a patent on FAHF-2. Dr Yang reported receiving research support from DBV Technologies during the conduct of the study. Dr Sussman reported receiving research support and consulting fees from DBV Technologies during the conduct of the study, as well as grants, consulting fees, and research support from Novartis; grants, consulting fees, and speaker fees from Aralez; consulting fees and research support from Merck, BioCryst, CSL Behring, and Dyax; grants and research support from Genentech; consulting fees from Pfizer; research support from GlaxoSmithKline, Stallergenes, GreenCross, and Kendrion; and grants from Aimmune Therapeutics outside the submitted work. Dr Brown-Whitehorn reported receiving consulting fees from DBV Technologies outside the submitted work. Dr Leonard reported that her institution received research support during the conduct of the study from DBV Technologies; she received support as a board member and a research grant from Food Allergy Research and Education (FARE); and her institution received research support from Aimmune Therapeutics and DBV Technologies. Dr Pongracic received nonfinancial and other support from DBV Technologies during the conduct of the study, as well as other support related to investigator meetings from Aimmune Therapeutics and nonfinancial support from Genentech/Novartis outside the submitted work; and her institution received research funding from Aimmune Therapeutics. Dr Assa'ad reported that her institution received research support and nonfinancial support from DBV Technologies during the conduct of the study, as well as research and nonfinancial support from Aimmune and Astellas outside the submitted work. Dr de Blay reported receiving grants and/or personal fees from Stallergenes Greer, Chiesi, ALK, Mundipharma, and Novartis, as well as serving as a board member for Stallergenes Greer, Novartis, ALK, Mundipharma, Meda Pharma, Boehringer, and AstraZeneca. Dr Bird reported receiving support for travel to meetings for the study or other purposes and his institution received research support during the conduct of the study from DBV Technologies; he received support as a board member at FARE, consultant fees from Aimmune Therapeutics and Wedbush Consulting, and speaking fees from Aimmune Therapeutics and DBV Technologies; and his institution received research support from Aimmune Therapeutics, DBV Technologies, the Foundation of the American College of Allergy, Asthma, and Immunology, and Nestle Health Sciences unrelated to the study. Dr Tilles reported receiving grants and/or personal fees from DBV Technologies, Aimmune, Astellas, Sanofi, Genentech, Immune Intolerance Network, Stanford University, Amgen, Circassia, Gilead, GlaxoSmithKline, Merck, Novartis, Pulmagen Therapeutics, Teva, Mylan, AstraZeneca, and FARE outside the submitted work. Dr Bourrier reported receiving personal fees from DBV Technologies during the conduct of the study, as well as nonfinancial support and/or personal fees from Stallergenes, Nestle, ALK, Mead Johnson, Novalac, and Thermo Fisher Scientific outside the submitted work. Dr Hebert reports receiving research support from DBV Technologies during the conduct of the study, as well as personal fees from GlaxoSmithKline, Merck, Novartis, Teva Pharmaceuticals, Shire, and CSL Behring outside the submitted work. Dr Green reported receiving research support from DBV Technologies during the conduct of the study, as well as research support and consultant fees from Aimmune Therapeutics and grants from FARE outside the submitted work. Dr Gerth van Wijk reported receiving grants from DBV Technologies during the conduct of the study, as well as personal fees from ALK-Abello, Allergopharma, and Novartis and grants from Biomay, STW, and the Netherlands Lung Foundation outside the submitted work. Dr Knulst reported receiving research support from DBV Technologies during the conduct of the study. Dr Kanny reported receiving research support from DBV Technologies during the conduct of the study. Dr Schneider reported receiving research support from DBV Technologies during the conduct of the study and serving on the Medical Advisory Board for FARE. Dr Dupont is cofounder of DBV Technologies, holds stock in DBV, and has received an honorarium for chairing DBV Technologies' Scientific Advisory Board. Dr Dupont also has patents related to a patch for screening the sensitivity state of patients with respect to an allergen and use thereof, immunotherapeutic method for increasing groundnut tolerance in a patient, and epicutaneous immunorebalancing. No other disclosures were reported. EDAT- 2017/11/15 06:00 MHDA- 2017/11/29 06:00 PMCR- 2018/05/14 CRDT- 2017/11/15 06:00 PHST- 2017/11/15 06:00 [entrez] PHST- 2017/11/15 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2018/05/14 00:00 [pmc-release] AID - 2662891 [pii] AID - jpc170007 [pii] AID - 10.1001/jama.2017.16591 [doi] PST - ppublish SO - JAMA. 2017 Nov 14;318(18):1798-1809. doi: 10.1001/jama.2017.16591.