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 L. 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: 60 IgE-mediated CMA children were enrolled. The proportion of children treated with AAF tolerant to the first exposure of EHCF+LGG was 0.98(exact 95% CI 0.91 to 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 to 0.67, n/N=14/29) than in the AAF group (0.03, 95% exact CI 0.001 to 0.17, n/N=1/30). There was an absolute benefit increase(ABI) of tolerance rate equal to 0.45(95% CI, 0.23 to 0.63, Newcombe method 10) for EHCF+LGG vs AAF, corresponding to a NNT of 2 (2 to 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.