- 2025-11-28
- Clinical and translational allergy 15(12)
- Barbara Cuomo
- Maria Carmen Verga
- Enza D'Auria
- Michele Miraglia Del Giudice
- Caterina Anania
- Fabio Decimo
- Giuliana Giannì
- Giovanni Cosimo Indirli
- Enrica Manca
- Filippo Mondì
- Valentina Nosratian
- Erica Pendezza
- Marco Ugo Andrea Sartorio
- Mauro Calvani
Study Design
- Type
- Review
- Population
- children with IgE-mediated milk allergy
- Methods
- systematic literature review and meta-analysis of controlled studies in accordance with PRISMA guidelines
Background
Milk ladder (ML) is considered a potential therapeutic option for managing cow's milk allergy (CMA). Although the ML was initially developed to reintroduce cow's milk into the diet for individuals with non-IgE mediated CMA, it has also recently been used in IgE-mediated CMA.Objective
To perform a systematic review and meta-analysis of the safety and efficacy of ML in children with IgE-mediated milk allergy.Methods
We conducted a systematic literature review and meta-analysis of controlled studies in accordance with PRISMA guidelines. ML safety and ML efficacy compared to a strict avoidance diet and oral immunotherapy in children with IgE mediated CMA was evaluated. Meta-analysis was performed where ≥ 3 studies reported data. Methodological quality and risk of bias were systematically assessed.Results
Six controlled studies (two randomized controlled trials and four observational controlled studies) met the inclusion criteria. ML resulted in the development of tolerance in 69% of participants (OR = 4.48; 95% CI = 2.51-8.00), with a significant improvement compared to the elimination diet. The meta-analysis of four studies showed that ML was 4.5 times more effective than a strict avoidance diet in inducing partial or total tolerance in ITT analysis and 8.4 times in PP analysis. Certainty of evidence was moderate, with low heterogeneity among studies. No significant difference in adverse events, severe systemic allergic reactions, and adrenaline use between the ML and avoidance diet groups were found. Only one study reported comparable efficacy between ML and oral immunotherapy with raw milk (OIT). No difference was found in the total number of mild to moderate adverse reactions between the groups (68.2% and 77.8, respectively; p = 0.44). The rates of epinephrine use at home were 14.3% and 11.8%, respectively, without significant difference between ML and OIT groups (p = 1).Conclusions
ML represents a promising therapeutic approach for accelerating tolerance in children with IgE-mediated CMPA. Further research is needed to clarify milk ladder safety, as well as to identify predictive biomarkers for patient selection.