Abstract
BACKGROUND: Asthma prevalence is increasing in the Asia-Pacific region. China and India account for > 35% of the world's population and are often underrepresented in clinical studies. This phase 3 study (NCT03782532) evaluated efficacy and safety of dupilumab, a monoclonal antibody blocking interleukin-4/13 signalling, in patients with persistent asthma from China and India. METHODS: Patients (≥ 12 years) were randomised 1:1 to dupilumab 200 mg or matched placebo every 2 weeks for 24 weeks (primary analysis population: blood eosinophils ≥ 150 cells/μL or fractional exhaled nitric oxide ≥ 25 parts per billion without maintenance oral corticosteroid [OCS]; OCS maintenance population: 300 mg OCS). PRIMARY ENDPOINT: change from baseline to week 12 in forced expiratory volume in 1 s (FEV(1)). Secondary endpoints: change from baseline to week 24 in 5-item Asthma Control Questionnaire (ACQ-5/7) scores, annualised severe exacerbation rate, and safety. RESULTS: In the primary analysis population (n = 414), change in FEV(1) by week 12 was significantly greater for dupilumab versus placebo (least squares mean difference: 0.31 L [95% CI: 0.23-0.39]; p < 0.0001). At week 24, greater reductions in ACQ-5 score were seen for dupilumab versus placebo (least squares mean difference: -0.20 [95% CI: -0.35 to -0.05]; p = 0.0097). Dupilumab reduced severe exacerbation risk by 62% versus placebo during the treatment period (relative risk: 0.38 [95% CI: 0.21-0.70]; nominal p = 0.002). Safety was similar between treatment arms; injection-site reactions were more common with dupilumab treatment (5.0%) than with placebo (1.2%). The OCS maintenance population showed similar outcomes. CONCLUSION: Dupilumab significantly improved lung function and asthma control, numerically reduced asthma exacerbations, and was well tolerated in patients from China and India with persistent asthma and evidence of either type 2 inflammation or OCS maintenance. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03782532.