Add-on mepolizumab in patients with severe asthma on medium-dose inhaled corticosteroids.

BACKGROUND: Mepolizumab is clinically beneficial for patients with severe asthma with an eosinophilic phenotype (SA-EP) but lacks randomised controlled trial efficacy data in those on medium-dose inhaled corticosteroids (ICS). This analysis assessed mepolizumab's efficacy in a subgroup of patients on medium-dose ICS from a Chinese phase 3 trial (NCT03562195). METHODS: Eligible SA-EP patients had received daily ≥500 µg·day-1 fluticasone propionate or equivalent. In this post hoc evaluation, we included patients who were on baseline medium-dose ICS. Outcomes assessed were rate of clinically significant exacerbations (CSEs) at week 52, time to first CSE, St George's Respiratory Questionnaire (SGRQ) score, pre-bronchodilator forced expiratory volume in 1 s (FEV1), asthma control questionnaire-5 (ACQ-5) score and rate of clinical remission. RESULTS: At week 52, in the medium-dose ICS subgroup, mepolizumab (n=115) versus placebo (n=104) significantly reduced the rate of CSEs (0.53 versus 1.30 events·yr-1; rate ratio 0.41 (95% CI 0.25-0.66); p<0.001), with a lower probability of CSE (Kaplan-Meier estimate, 27.0% versus 49.3%; HR 0.47 (95% CI 0.30-0.73); p<0.001), greater improvements, as measured by difference in least-square mean, in SGRQ score (-5.58, 95% CI -10.73 to -0.44), FEV1 (119.06 mL, 95% CI 6.66-231.45) and ACQ-5 score (-0.25, 95% CI -0.46 to -0.04), and a higher proportion of patients achieving three- or four-component clinical remission (31.3-57.4% versus 13.5-36.5%). The rate of clinical remission was higher in patients on medium-dose ICS than those on high-dose ICS. CONCLUSIONS: Mepolizumab provided greater clinical benefit across multiple outcomes including clinical remission versus placebo in Chinese SA-EP patients on medium-dose ICS. Earlier treatment could increase the chance of clinical remission.