Efficacy and Safety of Biologics, Allergen Immunotherapy, and Pharmacotherapies for Moderate‐to‐Severe Allergic Rhinitis: A Network Meta‐Analysis

BACKGROUND: The management of moderate-to-severe allergic rhinitis (AR) is challenging given numerous advanced therapies. A comparative, evidence-based treatment hierarchy to guide the selection of biologics, allergen immunotherapy (AIT), and advanced pharmacotherapies is critically lacking due to a paucity of head-to-head trials. This network meta-analysis established a treatment hierarchy for moderate-to-severe AR by comparing the efficacy and safety of biologics, AIT, and key pharmacotherapies. METHODS: We analyzed 28 randomized controlled trials (13,312 participants), which evaluated the efficacy and safety of biologics (anti-IgE, anti-IL-4Rα therapies), AIT (evaluated within a 6-month time frame to ensure comparability), and key pharmacotherapies (intranasal corticosteroids alone or combined with antihistamines) for moderate-to-severe AR. Efficacy was assessed by changes in the Total Nasal Symptom Score (TNSS), the Total Ocular Symptom Score (TOSS), and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). A treatment hierarchy was established using surface under the cumulative ranking curve (SUCRA) probabilities. RESULTS: For the TNSS, anti-IL-4Rα therapy was most effective, followed by anti-IgE therapy and AIT, which surpassed all pharmacotherapies. The combination of intranasal corticosteroid and intranasal antihistamine ranked the highest for ocular symptoms. Anti-IL-4Rα therapy was also superior for improving the RQLQ. Overall, all treatments demonstrated a favorable safety profile. Biologics and AIT did not show a significant increase in adverse events risk compared to placebo. CONCLUSIONS: This network meta-analysis establishes the first comprehensive treatment hierarchy for moderate-to-severe AR. Our findings demonstrate that biologics, particularly anti-IL-4Rα therapy, are the most effective interventions for nasal symptom control, ranking superior to AIT and pharmacotherapies, thus providing a robust, data-driven framework to personalize patient care.