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Mepolizumab, a humanised monoclonal antibody that targets interleukin\u20105, a key cytokine in type 2 inflammation, is an effective, approved treatment both in SAEP and CRSwNP. We aimed to analyse real\u2010world evidence of mepolizumab effectiveness in patients with comorbid SAEP and CRSwNP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study pooled five existing, predominantly European cohorts to describe the impact of mepolizumab on the rate of clinically significant exacerbations (CSEs) and other outcomes in adults with SAEP without and with comorbid CRSwNP (SAEP[\u2212]CRSwNP and SAEP[+]CRSwNP, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, 1037 patients were included. Baseline characteristics were similar in both cohorts. Mepolizumab was associated with a reduction from baseline in the annual rate of CSEs at 12\u2010months post\u2010initiation (SAEP[\u2212]CRSwNP: 72.7%; SAEP[+]CRSwNP: 79.7%), irrespective of baseline blood eosinophil count (BEC). When patients with SAEP[+]CRSwNP were compared with patients with SAEP[\u2212]CRSwNP, a 30.0% incremental benefit in the reduction of CSEs was observed. At 12\u2010months post\u2010initiation, mepolizumab was also associated with a reduction in oral corticosteroid use and BEC, and an improvement in lung function and Asthma Control Test (ACT) scores in both cohorts. Post\u2010mepolizumab initiation, \u2265\u20093 clinical remission criteria were fulfilled by 47.2% and 52.3% of patients with SAEP[\u2212]CRSwNP and SAEP[+]CRSwNP, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results provide a greater understanding of mepolizumab's effectiveness, demonstrating a substantial improvement in asthma outcomes, irrespective of baseline BEC and the presence of comorbid CRSwNP.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.16618","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T06:14:37Z","timestamp":1751350477000},"page":"2557-2571","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Mepolizumab Effectiveness in Severe Asthma With\/Without Chronic Rhinosinusitis With Nasal Polyps: Real\u2010World Pooled 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