Abstract
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.
Highlights
IntroductionSevere asthma is believed to affect 5–10% of all patients with asthma and encompasses heterogeneous subtypes which either require high-dose controller therapy or are refractory to current therapy.[1,2,3,4,5] Severe eosinophilic asthma is one phenotype, characterised by persistent eosinophilic inflammation and recurrent exacerbations which are not alleviated despite current standard of care.[1,6] While exacerbations are the primary outcome of many Phase III trials for biologics[7,8,9,10] and important in terms of patient welfare and direct costs, further outcomes are clinically important
Analysis of time to first asthma worsening during Part C demonstrated a 71% increased risk for patients who stopped mepolizumab relative to those who continued mepolizumab, over the 52-week treatment period (Hazard Ratio [HR]: 1.71 [95% confidence interval (CI) 1.17,2.52]; p=0.006) (Figure 1)
These analyses support and extend findings from the primary manuscript,[10] demonstrating that benefits gained from long-term mepolizumab therapy in patients with severe eosinophilic asthma are not maintained after stopping mepolizumab treatment
Summary
Severe asthma is believed to affect 5–10% of all patients with asthma and encompasses heterogeneous subtypes which either require high-dose controller therapy or are refractory to current therapy.[1,2,3,4,5] Severe eosinophilic asthma is one phenotype, characterised by persistent eosinophilic inflammation and recurrent exacerbations which are not alleviated despite current standard of care.[1,6] While exacerbations are the primary outcome of many Phase III trials for biologics[7,8,9,10] and important in terms of patient welfare and direct costs, further outcomes are clinically important. Mepolizumab, a humanised monoclonal antibody that binds to and neutralises interleukin-5, reducing eosinophil proliferation, activation and survival,[14,15] is approved for the treatment of severe eosinophilic asthma and eosinophilic granulomatosis with polyangiitis in multiple regions worldwide and for hypereosinophilic syndrome and chronic rhinosinusitis with nasal polyposis in the USA.[14,16,17] Several studies have demonstrated the long-term benefit and tolerability of mepolizumab compared with placebo in patients with severe eosinophilic asthma, showing efficacy in reducing exacerbations, improving lung function, reducing daily oral corticosteroid (OCS) dose and improving health-related quality of life (HRQoL).[18,19,20,21,22,23,24]
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