Efficacy and safety of baked milk oral immunotherapy in children with severe milk allergy: A randomized, double-blind, placebo-controlled phase 2 trial

Background: Cow's milk allergy is the most common food allergy in young children and has no current treatment. Oral immunotherapy studies to date have shown efficacy but high rates of adverse reactions. Objective: We sought to evaluate the safety and efficacy of baked milk oral immunotherapy (BMOIT) in children allergic to baked milk. Methods: Participants (3-18 years) were randomized to receive BMOIT or placebo for 12 months. Efficacy was assessed by double-blind placebo-controlled food challenge after 12 months of treatment. Safety, quality of life, and mechanistic parameters were also evaluated. Results: Eleven of 15 (73%) BMOIT participants reached the primary end point, tolerating 4044 mg of baked milk protein after 12 months of oral immunotherapy, compared with 0 of 15 (0%) on placebo. The median maximum tolerated dose and median change from baseline was significantly higher in the BMOIT group than in the placebo group (median maximum tolerated dose, 4044 mg vs 144 mg; P = .001; median change in maximum tolerated dose of 3900 mg vs 0 mg, P = .0001). Dose-related reactions were common, but more than 95% in both groups were mild. There was no significant change in cow's milk– or beta lactoglobulin–IgE from baseline for either group. Cow's milk-sIgG₄ did significantly increase and casein IgE decreased in the BMOIT group. For proxy-reported food allergy quality of life, there was a significant difference in the emotional impact domain only, with more improving while on placebo compared with BMOIT. Most children and adolescents in the BMOIT group directly reported improvement in at least 1 domain. Conclusions: BMOIT was well tolerated and induced a substantial level of desensitization after 12 months of treatment.