Rapid food desensitization supported by omalizumab, with adjunctive dupilumab for type 2 comorbidities: A pediatric case series.

Background: The therapeutic landscape of IgE-mediated food allergy is expanding, and Rapid Food Desensitization (RFD) has been proposed as an optional and innovative procedural strategy to provide rapid protection in selected high-risk patients. However, real-world evidence integrating RFD with biologic therapy remains scarce, and its optimal role within contemporary management strategies is still evolving. Objective: To describe a real-world pediatric case series of RFD supported by targeted biologic therapy in children with severe IgE-mediated food allergy, including those with additional Type 2 inflammatory multimorbidities. Methods: We conducted a prospective real-world case series of 3 consecutive pediatric cases managed under a standardized institutional RFD protocol. Clinical data were collected prospectively at each visit and during RFD using a standardized clinical report form within REDCap. All patients received omalizumab prior to RFD, and those with prominent Type 2-driven diseases also received dupilumab. Clinical evolution, desensitization outcomes, safety, and maintenance of daily ingestion following transition to oral immunotherapy (OIT) were evaluated. Results: All 3 patients had a history of severe food-induced anaphylaxis, and 2 had clinically relevant Type 2 multimorbidities (atopic dermatitis or eosinophilic esophagitis). Omalizumab enabled RFD to be performed safely by suppressing the immediate IgE-mediated response, while dupilumab was used reactively in selected cases to control persistent Type 2 inflammation. All patients achieved successful desensitization without severe breakthrough reactions and subsequently transitioned to OIT. At latest follow-up, all maintained daily ingestion of desensitized foods, with only mild, manageable symptoms in 1 case. Conclusion: This real-world pediatric case series suggests that RFD, when supported by omalizumab, is a feasible, safe, and innovative-yet optional-procedural approach for carefully selected high-risk patients. Omalizumab facilitated rapid protection, and targeted use of dupilumab may provide additional benefit in patients with overlapping Type 2 inflammatory pathways. Given the very small sample size and absence of a control group, these findings are hypothesis-generating. Larger, rigorously designed prospective studies are needed to refine patient selection, timing of biologics, and long-term outcomes of this evolving strategy.