Asthma worsening and symptom control are clinically important health outcomes in patients with severe eosinophilic
asthma. This analysis of COMET evaluated whether stopping versus continuing long-term
mepolizumab therapy impacted these outcomes. Patients with severe eosinophilic
asthma with ≥3 years continuous
mepolizumab treatment (via COLUMBA (NCT01691859) or COSMEX (NCT02135692) open-label studies) were eligible to enter COMET (NCT02555371), a randomised, double-blind, placebo-controlled study. Patients were randomised 1:1 to continue
mepolizumab 100 mg subcutaneous every 4 weeks or to stop
mepolizumab, plus standard of care
asthma treatment. Patients could switch to open-label
mepolizumab following an exacerbation. Health outcome endpoints included time to first
asthma worsening (composite endpoint: rescue use, symptoms, awakening at night and morning peak expiratory flow (PEF)), patient and clinician assessed global rating of
asthma severity and overall perception of response to
therapy, and unscheduled healthcare resource utilisation. Patients who stopped
mepolizumab showed increased risk of and shorter time to first
asthma worsening compared with those who continued
mepolizumab (hazard ratio (HR) 1.71; 95% CI 1.17-2.52; p=0.006), including reduced
asthma control (increased risk of first worsening in rescue use (HR 1.36; 95% CI 1.00-1.84; p=0.047) and morning PEF (HR 1.77; 95% CI 1.21-2.59; p=0.003). There was a higher probability of any unscheduled healthcare resource use (HR 1.81; 95% CI 1.31-2.49; p<0.001), and patients and clinicians reported greater
asthma severity and less favourable perceived response to
therapy for patients who stopped versus continued
mepolizumab. These data suggest that patients with severe eosinophilic
asthma continuing long-term
mepolizumab treatment sustain clinically important improvements in health outcomes.