Biologic-assisted immunotherapy for pediatric food allergy: a systematic review

Background: Food allergies affect up to 8% of children and are a major cause of anaphylaxis, reduced quality of life, and healthcare use. Oral immunotherapy (OIT) can induce desensitization but is limited by adverse reactions, tolerability challenges, and variable long-term outcomes. Emerging biologic therapies- particularly omalizumab and dupilumab- may improve the safety and efficiency of desensitization when used alone or with immunotherapy. Objective: To systematically review evidence on biologic-assisted immunotherapy and alternative desensitization approaches in pediatric food allergy, focusing on efficacy, sustained unresponsiveness, safety, treatment efficiency, and clinical applicability. Methods: A systematic review following PRISMA 2020 guidelines was conducted using PubMed, with supplementary searches of Google Scholar and SciSpace (2015-2025), to identify interventional studies of biologic therapies, OIT, sublingual immunotherapy (SLIT), epicutaneous immunotherapy (EPIT), and combination approaches in children < 18 years with IgE-mediated food allergy. Studies were synthesized using a narrative qualitative approach. Desensitization was defined as increased tolerated dose during active therapy; reaction threshold as the dose provoking symptoms; sustained unresponsiveness (SU) as absence of symptoms after treatment cessation; and tolerance as durable long-term nonreactivity independent of therapy. Risk of bias for randomized trials was assessed using the Cochrane Risk of Bias 2 (RoB2) tool. Results: Of 505 records, 17 studies met inclusion criteria. Omalizumab-assisted OIT demonstrated higher desensitization rates (approximately 67%-85%) and fewer adverse events compared with OIT alone (approximately 30%-40%), though effect sizes varied. Dupilumab showed modest improvements in tolerability with smaller effects on desensitization. Omalizumab monotherapy increased reaction thresholds across multiple allergens. SLIT and EPIT demonstrated favorable safety with moderate efficacy, particularly in younger children. Conclusion: Evidence suggests biologic-assisted immunotherapy- particularly omalizumab with OIT- may improve desensitization and safety in pediatric food allergy, though findings are limited by heterogeneity, sample size, and risk of bias. Larger trials are needed to confirm long-term durability, optimize protocols, and assess cost-effectiveness. SLIT and EPIT may offer safer alternatives for selected high-risk populations.