Continued long-term mepolizumab in severe eosinophilic asthma protects from asthma worsening versus stopping mepolizumab: COMET trial

Background: The long-term efficacy and safety of mepolizumab in severe eosinophilic asthma (SEA) have been shown. Aims: To assess the impact of stopping versus continuing long-term mepolizumab on asthma worsening. Methods: COMET (NCT02555371) was a randomised, double-blind, placebo-controlled study. Patients had completed COLUMBA (NCT01691859) or COSMEX (NCT02135692), had continuous mepolizumab for ≥3 years (mean 46.6 months), and stayed on asthma controller therapy. Randomisation was 1:1 to stop (switch to placebo) or continue subcutaneous mepolizumab 100 mg for 52 weeks. Composite endpoint: time to first asthma worsening (defined in Table). Daily eDiary data were analysed using Kaplan–Meier estimates and a Cox proportional hazards model adjusted for covariates. Results: Treatment differences for those who stopped versus continued mepolizumab emerged by Week 4 (8 weeks post last open-label mepolizumab dose). For those who stopped mepolizumab, 51.7% reported asthma worsening by Week 52 versus 35.0% who continued mepolizumab (Table), leading to a significantly shorter time to first asthma worsening in those who stopped mepolizumab. Conclusion: Stopping mepolizumab in patients with SEA led to an increased risk of asthma worsening with a significantly shorter time to first asthma worsening versus those continuing long-term mepolizumab. Funding: GSK [201810/NCT02555371].