Varying Doses of Epicutaneous Immunotherapy With Viaskin Milk vs Placebo in Children With Cow’s Milk Allergy

Abstract

ImportanceNo approved treatment exists for allergen-specific immunoglobulin E (IgE)–mediated cow’s milk allergy (CMA), a common childhood food allergy.ObjectiveTo assess dose, efficacy, and safety of epicutaneous immunotherapy with Viaskin milk in children with IgE-mediated CMA.Design, Setting, and ParticipantsA 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 μg, 300 μg, or 500 μg 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.InterventionSafety of Viaskin milk (150-μg, 300-μg, or 500-μg 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 μg, 300 μg, or 500 μg or placebo (1:1:1:1) for 12 months.Main Outcomes and MeasuresThe 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.ResultsA 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-μg 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-μg Viaskin milk dose group experienced treatment-related anaphylaxis.Conclusions and RelevanceIn this randomized clinical trial, 12 months of daily epicutaneous immunotherapy with a dose of Viaskin milk at 300 μg 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 RegistrationClinicalTrials.gov Identifier: NCT02223182

Errors in Abstract, Key Points, Text, Figures, and Additional Contributions

“…In the Original Investigation titled “Varying Doses of Epicutaneous Immunotherapy With Viaskin Milk vs Placebo in Children With Cow’s Milk Allergy: A Randomized Clinical Trial,” published online February 26, 2024, and in the April 2024 issue of JAMA Pediatrics , the Abstract, Key Points, and text’s introduction were corrected to add “allergen-specific”; to fix typographical errors in the Methods; to capitalize “Viaskin Milk” throughout the article; to correct the number of children who received the 500-μg dose of Viaskin Milk to 36 in Figure 1; to add the following omitted sentence to the Results: “Changes were less marked for CM-specific IgE (with no significant trends to the component proteins), and there was an increase in the Viaskin Milk 300-µg group only from baseline to month 3, followed by a decrease below the month 0 value at month 12”; to fix panel and axis labels in Figure 3; and to add Additional Contributions that had been inadvertently omitted. This article was corrected online.…”