Comparative Efficacy of Combined and Standalone Oral Immunotherapies for Peanut Allergy: a Bayesian Network Meta-Analysis of RCTs.

BACKGROUND: Peanut allergy is a chronic IgE-mediated disease with potentially life-threatening consequences. While several immunotherapeutic strategies have emerged, including oral immunotherapy (OIT), omalizumab (OMA)-based therapies, and probiotic and peanut oral immunotherapy (PPOIT), the comparative effectiveness of these interventions remains unclear. This study aimed to evaluate the relative efficacy and safety of combined and standalone oral immunotherapies for peanut allergy using a Bayesian network meta-analysis (NMA). METHODS: A systematic literature search was conducted in PubMed, EMBASE, and Web of Science up to March 2025. We included randomized controlled trials (RCTs) involving patients with IgE-mediated peanut allergy who received OIT + OMA, OMA monotherapy, OIT alone, or PPOIT. Outcomes included low-dose and high-dose desensitization, sustained unresponsiveness (SU), and safety outcomes (adverse events, AEs). The risk of bias was assessed using RoB 2. Analyses were performed using R software (version 4.4.3) with Bayesian NMA methods. RESULTS: Nineteen RCTs involving 2040 participants were included. Based on Probability Scores (P-scores), OIT + OMA demonstrated the highest efficacy for both low- (P-score: 97.20%) and high-dose desensitization (96.69%), followed by PPOIT (70.15% and 51.16%), OIT third (64.40% and 52.72%), and OMA fourth (75.29% and 71.21%). PPOIT and OIT showed moderate efficacy for SU. OIT was associated with a higher frequency of AEs compared with placebo. CONCLUSIONS: Combination and modified immunotherapies may offer improved efficacy and safety profiles, though results should be interpreted in the context of limited data and study heterogeneity.