Rheumatic adverse events associated with biologic therapy for chronic rhinosinusitis: A systematic review and meta‐analysis

Abstract Background Biologic therapies approved for treating chronic rhinosinusitis with nasal polyps (CRSwNP) have well‐established safety profiles but reports of rheumatic adverse events (AEs) are increasing and not well defined. This review aims to assess the risk and incidence of rheumatic AEs associated with biologic therapy in CRSwNP and summarize current reported management strategies. Methods A protocol was registered in PROSPERO [CRD42024525663]. A search was conducted in four electronic databases: Medline (Ovid), Embase, Scopus, and Cochrane CENTRAL from inception until January 4, 2024. Two reviewers independently screened citations and extracted data. Methodological quality was assessed using the Joanna Briggs Institute's critical appraisal tool. Data were pooled using a random effects model to calculate overall incidence and relative risk. Results Twenty‐one studies met the final inclusion criteria, totaling 3434 patients of which 2763 (80%) received either dupilumab ( n = 2257; 82%), mepolizumab ( n = 372; 13%), or omalizumab ( n = 134; 5%) for treatment of CRSwNP. The overall incidence rate for any on‐treatment rheumatic AE was 0.05 per person–year (95% CI, 0.03–0.09, I 2 = 75%). Biologic therapy increased the risk of developing a rheumatic AE (RR = 2.53; 95% CI, 1.29–4.94) compared with placebo. The most frequently reported rheumatic AE was arthralgia or joint pain ( n = 94; 95%), followed by lupus‐like syndrome or lupus erythematosus‐like reaction ( n = 2; 2.5%). Discontinuation of treatment was the most common intervention ( n = 21, 39%). Conclusion Biologic therapy increases the risk of rheumatic AEs in CRSwNP patients by over twofold. Healthcare providers should remain vigilant in monitoring rheumatic AEs and apply appropriate management strategies on a case‐by‐case basis.