(1) Background: Allergic rhinitis (AR) is a common disease in otolaryngology and novel biological therapies are required for clinical needs. To assess the tolerability of monoclonal antibodies, justifying their clinical applications, we presented a comprehensive safety profile of biologics in AR; (2) Methods: A systematic literature search was conducted following PRISMA guidelines for randomized clinical trials comparing monoclonal antibodies and placebo in AR. PubMed, Web of Science, Medline, and Cochrane were searched up until 9 January 2023. Among 3590 records in total, 12 studies with more than 2600 patients were included. Quality was assessed for all studies using Cochrane risk-of-bias tool for randomized trials, and subgrouped meta-analysis was performed; (3) Results: We accomplished an up-to-date literature overview and analysis on adverse events of monoclonal antibodies in AR. Total, common, severe, discontinuation-causing, and serious adverse events failed to reach statistical significance. Country was an essential factor for heterogeneity, and urticaria was the adverse event at highest risk (RR 2.81, 95% CI 0.79–9.95); (4) Conclusions: Monoclonal antibodies are considered well tolerated and relatively safe in patients with AR. The regions of patients and hypersensitive adverse reactions such as urticaria require a special caution in biological treatments in AR.
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