The step‐down approach in children with cow's milk allergy: Results of a randomized controlled trial

Background The Step‐Down Approach for Cow's Milk Allergy (SDACMA) trial evaluated the tolerability and the rate of immune tolerance acquisition in CMA children starting dietary treatment with amino acid‐based formula (AAF) and then switching to EHCF containing the probiotic Lacticaseibacillus rhamnosus GG (EHCF + LGG). Methods Randomized controlled trial involving IgE‐mediated CMA children receiving AAF from at least 4 weeks. EHCF + LGG tolerance was evaluated by the results of double‐blind placebo‐controlled food challenge (DBPCFC). Subjects tolerating EHCF + LGG were randomly allocated to remain on AAF, or to switch to EHCF + LGG. Immune tolerance acquisition to cow's milk proteins was evaluated with DBPCFC after 12 months of treatment. Allergy screening tests and body growth were also monitored. Results Sixty IgE‐mediated CMA children were enrolled. The proportion of children treated with AAF who resulted tolerant to the first exposure of EHCF + LGG was 0.98 (exact 95% CI 0.91–0.99). The rate of the immune tolerance acquisition to cow milk proteins after 12 months treatment was higher in the EHCF + LGG (0.48, 95% exact CI 0.29–0.67, n/N = 14/29) than in the AAF group (0.03, 95% exact CI 0.001–0.17, n/N = 1/30). There was an absolute benefit increase (ABI) of tolerance rate equal to 0.45 (95% CI 0.23–0.63, Newcombe method 10) for EHCF + LGG versus AAF, corresponding to a NNT of 2 (2–4, Bender's method). A normal body growth pattern was observed in the two study groups. Conclusion In IgE‐mediated CMA children the step‐down from AAF to EHCF + LGG is well tolerated and could facilitate the immune tolerance acquisition. The SDACMA trial evaluated the tolerability and the rate of immune tolerance acquisition in CMA children starting dietary AAF treatment and then switching to EHCF + LGG. Subjects tolerating EHCF + LGG were randomly allocated to remain on AAF, or to switch to EHCF + LGG. In IgE‐mediated CMA children the step‐down from AAF to EHCF + LGG is well tolerated and could facilitate the immune tolerance acquisition.Abbreviations: AAF, amino acid‐based formula; CMP: cow’s milk protein; DBPCFC, double‐blind placebo‐controlled food challenge; EHCF+LGG, extensively hydrolyzed casein formula plus Lactobacillus rhamnosus GG; IgE, immunoglobulin E; SDACMA, Step‐Down Approach in children with Cow’s Milk Allergy; SPT, skin prick test