PMID- 38407859
OWN - NLM
STAT- MEDLINE
DCOM- 20240403
LR  - 20240513
IS  - 2168-6211 (Electronic)
IS  - 2168-6203 (Print)
IS  - 2168-6203 (Linking)
VI  - 178
IP  - 4
DP  - 2024 Apr 1
TI  - Varying Doses of Epicutaneous Immunotherapy With Viaskin Milk vs Placebo in 
      Children With Cow's Milk Allergy: A Randomized Clinical Trial.
PG  - 345-353
LID - 10.1001/jamapediatrics.2023.6630 [doi]
AB  - IMPORTANCE: No approved treatment exists for allergen-specific immunoglobulin E 
      (IgE)-mediated cow's milk allergy (CMA), a common childhood food allergy. 
      OBJECTIVE: To assess dose, efficacy, and safety of epicutaneous immunotherapy 
      with Viaskin milk in children with IgE-mediated CMA. DESIGN, SETTING, AND 
      PARTICIPANTS: A phase 1/2, 2-part, randomized, double-blind, placebo-controlled 
      dose-ranging clinical trial in children aged 2 to 17 years with IgE-mediated CMA 
      was conducted between November 2014 through December 2017. It took place at 17 
      trial sites in the US and Canada. Current CMA was confirmed by double-blind, 
      placebo-controlled food challenge at study entry. Part A assessed the short-term 
      safety of 150 mug, 300 mug, or 500 mug of Viaskin milk; part B evaluated the 
      efficacy and safety of the 3 doses vs placebo over 12 months of treatment. Of the 
      308 screened participants with physician-diagnosed CMA, 198 met eligibility 
      criteria (including an eliciting dose 300 mg or less) and were randomized. 
      INTERVENTION: Safety of Viaskin milk (150-mug, 300-mug, or 500-mug doses) was 
      evaluated over a 3-week period (part A). In part B, 180 additional participants 
      were randomized to receive Viaskin milk at doses of 150 mug, 300 mug, or 500 mug or 
      placebo (1:1:1:1) for 12 months. MAIN OUTCOMES AND MEASURES: The primary outcome 
      was the proportion of treatment responders, defined as a 10-fold or more increase 
      in the cumulative reactive dose of cow's milk protein (reaching at least 144 mg) 
      or a cumulative reactive dose of cow's milk protein at 1444 mg or more at the 
      month 12 double-blind, placebo-controlled food challenge. RESULTS: A total of 
      95.5% of the randomized participants (mean [SD] age, 8 [4.17] years; 124 of 198 
      were male [62.6%]) completed treatment. The highest response rate was observed in 
      participants who received Viaskin milk at the 300-mug dose with 24 of 49 
      responders (49.0%) overall vs 16 of 53 responders (30.2%) in the placebo group 
      (odds ratio, 2.19; 95% CI, 0.91-5.41; P = .09), highest in the 2 to 11 years age 
      group (22 of 38 [57.9%] vs 13 of 40 [32.5%]; P = .04). Most treatment-emergent 
      adverse events were mild or moderate application-site reactions. One participant 
      in the 500-mug Viaskin milk dose group experienced treatment-related anaphylaxis. 
      CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, 12 months of daily 
      epicutaneous immunotherapy with a dose of Viaskin milk at 300 mug was associated 
      with a statistically significant treatment response in 2- to 11-year-old children 
      with IgE-mediated CMA. Treatment-related anaphylaxis and treatment-related 
      discontinuation rates were low. Further research is needed to explore Viaskin 
      milk as a viable treatment option for children with IgE-mediated CMA. TRIAL 
      REGISTRATION: ClinicalTrials.gov Identifier: NCT02223182.
FAU - Petroni, Daniel
AU  - Petroni D
AD  - Seattle Allergy and Asthma Research Institute, Seattle, Washington.
FAU - Begin, Philippe
AU  - Begin P
AD  - Section of Allergy, Immunology and Rheumatology, Department of Pediatrics, CHU 
      Sainte-Justine, Montreal, Quebec, Canada.
FAU - Bird, J Andrew
AU  - Bird JA
AD  - University of Texas Southwestern Medical Center, Dallas.
FAU - Brown-Whitehorn, Terri
AU  - Brown-Whitehorn T
AD  - Children's Hospital of Philadelphia, Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia.
FAU - Chong, Hey J
AU  - Chong HJ
AD  - UPMC Children's Hospital of Pittsburgh and University of Pittsburgh School of 
      Medicine, Pittsburgh, Pennsylvania.
FAU - Fleischer, David M
AU  - Fleischer DM
AD  - Children's Hospital Colorado, University of Colorado Denver School of Medicine, 
      Aurora.
FAU - Gagnon, Remi
AU  - Gagnon R
AD  - Clinique Specialisee en Allergie de la Capitale, Quebec, Quebec, Canada.
FAU - Jones, Stacie M
AU  - Jones SM
AD  - Department of Pediatrics, Arkansas Children's Hospital, University of Arkansas 
      for Medical Sciences, Little Rock.
FAU - Leonard, Stephanie
AU  - Leonard S
AD  - Department of Pediatrics, Rady Children's Hospital, University of California, San 
      Diego.
FAU - Makhija, Melanie M
AU  - Makhija MM
AD  - Division of Allergy and Immunology, Ann and Robert H. Lurie Children's Hospital 
      of Chicago, Northwestern University Feinberg School of Medicine, Chicago, 
      Illinois.
FAU - Oriel, Roxanne C
AU  - Oriel RC
AD  - The Elliot and Roslyn Jaffe Food Allergy Institute, Division of Allergy and 
      Immunology, Department of Pediatrics, Kravis Children's Hospital, Icahn School of 
      Medicine at Mount Sinai, New York, New York.
FAU - Shreffler, Wayne G
AU  - Shreffler WG
AD  - Massachusetts General Hospital, Boston.
FAU - Sindher, Sayantani B
AU  - Sindher SB
AD  - Stanford University, Palo Alto, California.
FAU - Sussman, Gordon L
AU  - Sussman GL
AD  - Gordon Sussman Clinical Research, Toronto, Ontario, Canada.
FAU - Yang, William H
AU  - Yang WH
AD  - Department of Medicine, Ottawa Allergy Research Corporation, University of Ottawa 
      Medical School, Ottawa, Ontario, Canada.
FAU - Bee, Katharine J
AU  - Bee KJ
AD  - DBV Technologies SA, Montrouge, France.
FAU - Bois, Timothee
AU  - Bois T
AD  - DBV Technologies SA, Montrouge, France.
FAU - Campbell, Dianne E
AU  - Campbell DE
AD  - DBV Technologies SA, Montrouge, France.
AD  - Westmead Children's Hospital, Westmead, New South Wales, Australia.
FAU - Green, Todd D
AU  - Green TD
AD  - UPMC Children's Hospital of Pittsburgh and University of Pittsburgh School of 
      Medicine, Pittsburgh, Pennsylvania.
AD  - DBV Technologies SA, Montrouge, France.
FAU - Rutault, Karine
AU  - Rutault K
AD  - DBV Technologies SA, Montrouge, France.
FAU - Sampson, Hugh A
AU  - Sampson HA
AD  - DBV Technologies SA, Montrouge, France.
AD  - Division of Allergy and Immunology, Department of Pediatrics, Icahn School of 
      Medicine at Mount Sinai, New York, New York.
FAU - Wood, Robert A
AU  - Wood RA
AD  - Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland.
LA  - eng
SI  - ClinicalTrials.gov/NCT02223182
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - United States
TA  - JAMA Pediatr
JT  - JAMA pediatrics
JID - 101589544
RN  - 0 (Allergens)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 0 (Milk Proteins)
SB  - IM
EIN - JAMA Pediatr. 2024 Apr 1;178(4):421. PMID: 38557707
EIN - JAMA Pediatr. 2024 May 13;:. PMID: 38739378
MH  - Animals
MH  - Cattle
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Humans
MH  - Infant
MH  - Male
MH  - Allergens
MH  - *Anaphylaxis
MH  - Immunoglobulin E
MH  - Immunotherapy
MH  - *Milk Hypersensitivity/therapy
MH  - Milk Proteins
PMC - PMC10897821
COIS- Conflict of Interest Disclosures: Dr Petroni reported support from the Seattle 
      Allergy and Asthma Research Institute during the conduct of the study and support 
      from DBV Technologies outside the submitted work. Dr Begin reported grants from 
      DBV Technologies during the conduct of the study; grants from DBV Technologies, 
      personal fees from DBV Technologies, Sanofi, ALK, Pfizer, Bausch Health, and 
      Novartis, and grants from Regeneron outside the submitted work. Dr Bird reported 
      grants from DBV Technologies during the conduct of the study; personal fees from 
      AllerGenis, Allergy Therapeutics, DBV Technologies, Genentech, Hanimmune 
      Therapeutics, HAL Allergy, Novartis, and Nutricia, grants from Aimmune, Astellas, 
      DBV Technologies, FARE, Genentech, the National Institutes of Health National 
      Institute of Allergy and Infectious Diseases, Novartis, Regeneron, and Siolta 
      outside the submitted work; and uncompensated organizational leadership roles 
      with the American Academy of Allergy, the Asthma and Immunology, American Academy 
      of Pediatrics Section on Allergy and Immunology, the International FPIES 
      Association, Vedanta, and the Texas Department of State Health Services Stock 
      Epinephrine Advisory Committee. Dr Brown-Whitehorn reported grants and personal 
      fees from DBV Technologies during the conduct of the study. Dr Fleischer reported 
      grants and consultant fees from DBV Technologies during the conduct of the study. 
      Dr Gagnon reported being a primary investigator for a DBV Technologies trial 
      during the conduct of the study. Dr Jones reported grants from DBV Technologies 
      during the conduct of the study; personal fees from Aimmune Therapeutics, grants 
      from Aimmune Therapeutics clinical trials, DBV Technologies, Regeneron, Novartis, 
      Genentech, Astellas, FARE Clinical Trials, and the National Institutes of Health 
      National Institute of Allergy and Infectious Diseases outside the submitted work. 
      Dr Leonard reported personal fees from DBV Technologies during the conduct of the 
      study; personal fees from Aimmune Therapeutics as an advisor, research support 
      from Aimmune Therapeutics, personal fees from Haimmune Therapeutics as an 
      employee, and personal fees from Cour Pharmaceuticals as member of DMC outside 
      the submitted work. Dr Makhija reported grants from DBV Technologies during the 
      conduct of the study. Dr Oriel reported grants from DBV Technologies during the 
      conduct of the study. Dr Shreffler reported personal fees from DBV Technologies 
      during the conduct of the study; and personal fees from Aimmune/Nestle and FARE 
      Clinical Trials outside the submitted work. Dr Sindher reported grants from DBV 
      Technologies during the conduct of the study; grants from Aimmune, CoFAR, the 
      National Institute of Allergy and Infectious Diseases, and Regeneron, and being a 
      member of a Genentech advisory board outside the submitted work. Dr Sussman 
      reported grants from DBV Technologies during the conduct of the study; grants 
      from Novartis, Amgen, Aslan Pharmaceuticals, Pharvaris, CSL Behring, AstraZeneca, 
      Innovaderm Research, Leo Pharma, KalVista Pharma, and DBV Technologies outside 
      the submitted work. Dr Bee reported employment by DBV Technologies. Dr Campbell 
      reported personal fees from DBV Technologies; personal fees from Allergenis 
      grants from the National Health and Medical Research Council of Australia outside 
      the submitted work. Dr Green reported being an employee of DBV Technologies, and 
      prior to joining DBV Technologies, was site principal investigator for the study 
      being reported while employed full time at UPMC Children's Hospital of 
      Pittsburgh. Dr Rutault reported being an employee of DBV Technologies. Dr Sampson 
      reported consulting fees and stock options from DBV Technologies during the 
      conduct of the study; personal fees from N-Fold, Siolta Therapeutics Scientific, 
      AbbVie Anaphylaxis Adjudication Committee, and stock options from N-Fold outside 
      the submitted work. Dr Wood reported grants from DBV Technologies during the 
      conduct of the study; grants from Aimmune, ALK, Genentech, Aravax, Siolta, and 
      the National Institute of Allergy and Infectious Diseases outside the submitted 
      work. No other disclosures were reported.
EDAT- 2024/02/26 12:44
MHDA- 2024/04/03 06:45
PMCR- 2024/02/26
CRDT- 2024/02/26 11:56
PHST- 2024/04/03 06:45 [medline]
PHST- 2024/02/26 12:44 [pubmed]
PHST- 2024/02/26 11:56 [entrez]
PHST- 2024/02/26 00:00 [pmc-release]
AID - 2815455 [pii]
AID - poi230097 [pii]
AID - 10.1001/jamapediatrics.2023.6630 [doi]
PST - ppublish
SO  - JAMA Pediatr. 2024 Apr 1;178(4):345-353. doi: 10.1001/jamapediatrics.2023.6630.