Efficacy of mepolizumab, an anti-interleukin-5 monoclonal antibody, was demonstrated in randomised, controlled trials; data on its real-world impact in routine clinical practice are starting to emerge. We assessed the effectiveness and safety of mepolizumab prescribed for patients in the real world.REALITI-A is a global, prospective, observational cohort study, collecting data from routine healthcare visits from patients with asthma. Patients newly prescribed mepolizumab for severe asthma with 12 months' relevant medical history pre-mepolizumab (collected retrospectively) were enrolled. An initial analysis of data from early initiators who had completed 1-year follow-up (as of 28 February 2019) was conducted. The primary objective was to compare the rate of clinically significant exacerbations (CSEs; requiring oral corticosteroids [OCS] and/or hospitalisation/emergency department [ED] visit) before and after mepolizumab; exacerbations requiring hospitalisation/ED visit and change in maintenance OCS use were secondary objectives. Treatment-related adverse events (AEs) were reported.Overall, 368 mepolizumab-treated patients were included. Rates of CSEs were reduced by 69% from 4.63/person/year pre-treatment to 1.43/person/year during follow-up (p<0.001), as were those requiring hospitalisation and/or ED visits (from 1.14/person/year to 0.27/person/year; 77% reduction). In 159 patients with maintenance OCS dose data available during the pre-treatment period, median daily dose decreased from 10.0 mg·day-1 (pre-treatment) to 5.0 mg·day-1 by Week 21-24 of follow-up, sustained until Week 53-56. No new safety signals were reported.These data demonstrate that the effectiveness of mepolizumab is consistent with clinical trial results under real-world settings, with significant reductions in exacerbations and daily maintenance OCS dose.