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

Petroni D, Bégin P, Bird JA, Brown-Whitehorn T, Chong HJ, Fleischer DM, Gagnon R, Jones SM, Leonard S, Makhija MM, Oriel RC, Shreffler WG, Sindher SB, Sussman GL, Yang WH, Bee KJ, Bois T, Campbell DE, Green TD, Rutault K, Sampson HA, Wood RA. JAMA Pediatr. 2024 Feb 26:e236630. doi: 10.1001/jamapediatrics.2023.6630

Key Points

Question  Was a safe and efficacious dose of Viaskin milk identified in this phase 1/2 clinical trial?

Findings  In this randomized clinical trial, a statistically significant treatment response was observed in children who received 12 months of daily epicutaneous immunotherapy (EPIT) with Viaskin milk at a dose of 300 μg compared with placebo, with no adverse safety signal observed.

Meaning  With no approved treatment for immunoglobulin E-mediated cow’s milk allergy, EPIT with Viaskin milk may be a viable therapeutic option, with potential to assess Viaskin milk in future clinical trials.

Abstract

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 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.

Intervention  Safety 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 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.

Median Changes From Month 0 to Month 12 of Specific Immunoglobulin E (IgE)
and IgG4to Caseins, Alpha-lactalbumin, and Beta-lactoglobulin by Treatment Group

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-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 Relevance  In 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.

PDF