Efficacy and safety of mepolizumab in a Chinese population with severe asthma: a phase III, randomised, double-blind, placebo-controlled trial
Ruchong Chen, Liping Wei, Yuanrong Dai, Zaiyi Wang, Danrong Yang, Meiling Jin, Cui Xiong, Ting Li, Shuling Hu, Jie Song, Robert Chan, Subramanya Kumar, Aya Abdelkarim, Nanshan Zhong
Abstract
Background In China, the prevalence of severe asthma with eosinophilic phenotype is rising, yet treatment options are limited. Mepolizumab is the first targeted biologic therapy for eosinophilic-driven disease in China. This study (clinicaltrials.gov identifier NCT03562195 ) evaluated efficacy and safety of mepolizumab in Chinese patients with severe asthma. Methods The phase III, multicentre, randomised, placebo-controlled, double-blind, parallel-group study enrolled patients aged ≥12 years with severe asthma, with two or more exacerbations in the previous year, and on inhaled corticosteroids plus at least one controller medication. Following a 1–4-week run-in, patients were randomised 1:1 to mepolizumab 100 mg or placebo subcutaneously every 4 weeks for 52 weeks. The primary end-point was annualised rate of clinically significant exacerbations (CSEs) through week 52. Secondary end-points were time to first CSE, frequency of CSEs requiring hospitalisation/emergency department visits or hospitalisation over 52 weeks, mean change in St George's Respiratory Questionnaire (SGRQ) total score and pre-bronchodilator forced expiratory volume in 1 s (FEV 1 ) at week 52; safety was evaluated. Results The modified intention-to-treat population included 300 patients. At week 52 with mepolizumab versus placebo, annualised rate of CSEs was 65% lower (0.45 versus 1.31 events per year; rate ratio 0.35, 95% CI 0.24–0.50; p<0.001); time to first CSE longer (hazard ratio 0.38, 95% CI 0.26–0.56; p<0.001) and number of CSEs requiring hospitalisation/emergency department visit lower (rate ratio 0.30, 95% CI 0.12–0.77; p=0.012). From baseline to week 52, SGRQ score improved (p=0.001) and pre-bronchodilator FEV 1 increased (p=0.006). Incidence of adverse events was similar between treatment groups. Conclusion Mepolizumab provided clinical benefits to patients with severe asthma in China and showed a favourable benefit–risk profile.