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AbstractObjectiveMethodsResultsConclusionAlthough the efficacy of mepolizumab in reducing exacerbations and oral corticosteroid (OCS) use in severe asthma is well-established, real-world long-term effectiveness data are limited. This study evaluated the real-world impact of mepolizumab treatment in patients with severe asthma over a 4-year follow-up period.This was a retrospective cohort study of patients with asthma initiating mepolizumab (index date: first claim, November 2015–September 2019) using the Merative MarketScan Commercial and Medicare Databases. Outcomes included asthma exacerbations, OCS use, and exacerbation-related healthcare resource utilization (HCRU) and costs, assessed 12-months pre-index (baseline) and annually during the 4-year follow-up period.Among 189 eligible patients, mean asthma exacerbation rate (AER) declined progressively from baseline during follow-up: AER decreased by 53.8% at Year 1 and 73.8% by Year 4 (p < 0.001). The annual OCS prescription rate reduced from baseline by 41.1% at Year 1 and 62.2% at Year 4 (p < 0.001). The proportion of patients with both no exacerbations and no OCS use progressively increased from 6.4% at baseline to 18.5% at Year 1 and 41.8% at Year 4. Exacerbation-related HCRU including inpatient, emergency room, and outpatient office visits decreased from baseline (9.0%, 21.7%, and 78.8%, respectively), at Year 1 (3.2%, 12.2%, and 49.2%), and Year 4 (0.0%, 4.8%, and 31.8%). Exacerbation-related healthcare costs declined from $4,635 at baseline to $1,487 at Year 1 and $217 at Year 4 (p < 0.001).Patients treated with mepolizumab demonstrated progressive and sustained long-term, real-world reductions in exacerbation frequency, OCS dependency, and exacerbation-related HCRU and costs over 4 years. [ABSTRACT FROM AUTHOR]