Efficacy and safety of mepolizumab in a Chinese population with severe asthma: a phase III, randomised, double-blind, placebo-controlled trial

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 (FEV₁) 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 FEV₁ 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.

FIGURE 1

Patient disposition. s.c.: subcutaneous.

FIGURE 2

Kaplan–Meier plots of time to first a) clinically significant exacerbation (CSE), b) CSE requiring hospitalisation and/or emergency department (ED) visits and c) CSE requiring hospitalisation (Chinese modified intention-to-treat population only). HR: hazard ratio. ^#: analysed using a Cox proportional hazards model, adjusting for covariates as described in the Mepolizumab as Adjunctive Therapy in Patients with Severe Asthma study [18].

FIGURE 3

a) Cumulative distribution of patients with ≥4-point improvement from baseline in total St George's Respiratory Questionnaire (SGRQ) score at week 52. b) Pre-bronchodilator forced expiratory volume in 1 s (FEV₁) change (95% CI) from baseline through week 52 (Chinese modified intention-to-treat population); placebo least-squares (LS) mean change±se at week 52: 125.67±35.49; mepolizumab LS mean change at week 52: 262.79±34.34; mean difference (95% CI) between mepolizumab and placebo at week 52: 137.13 (39.79–234.46), p=0.006 (analysed using mixed-model, repeated-measures method adjusting for covariates used in the Mepolizumab as Adjunctive Therapy in Patients with Severe Asthma study) [18]. ^#: missing data: 18 (11.9%) out of 151; ^¶: missing data: seven (4.7%) out of 149.