Mepolizumab is not inferior to omalizumab, improving asthma control in severe allergic and eosinophilic asthma, a randomised, blinded, non-inferiority trial.

<bold>Introduction</bold>; Biologic therapies are highly effective at improving outcomes in severe asthma with type 2 inflammation. There are no prospective comparative trials, and a large proportion of patients are eligible for multiple therapies. <bold>Aims</bold>; To determine if mepolizumab (Mepo) is non-inferior to omalizumab (Oma) for improving asthma control in severe allergic and eosinophilic asthma. <bold>Methods</bold>; an open label, randomised non-inferiority trial of adults with severe allergic and eosinophilic asthma, with poor control and severe exacerbations, despite optimised specialist care, were randomised with equal probability to receive 6 months therapy with either Mepo or Oma. The primary outcome was 6-month ACQ5. Non-inferiority would be declared if the mean, baseline-adjusted, 6-month ACQ5 for Mepo was no worse than the corresponding ACQ5 for Oma, by a pre-specified margin of 0.35. The statistician was blinded to treatment group. <bold>Results</bold>; At baseline, participants had poorly controlled asthma, mean (SD) ACQ5 of 3.02 (0.93; Mepo), 3.16 (1.11; Oma), and frequent exacerbations in the previous 12 months; Mepo, 4.3 (2.7). Oma, 4.7 (3.3). Eighty participants were included in the primary per-protocol analysis. At 6 months, ACQ5 was reduced by a mean 1.68 with Mepo and 1.62 with Oma. The baseline adjusted mean difference (Mepo-Oma) was −0.16, with two-sided 95% confidence interval (CI) (−0.62, 0.29). The 97.5% upper confidence limit was a 0.29, establishing non-inferiority of Mepo to Oma. <bold>Conclusions</bold>; In severe allergic and eosinophilic asthma treatment with Mepo is non-inferior to Oma at improving asthma control at 6 months.