Mepolizumab effectiveness and identification of super-responders in severe asthma
Erin S. Harvey, David Langton, Constance H. Katelaris, Sean Stevens, Claude S. Farah, Andrew Gillman, John Harrington, Mark Hew, Vicky Kritikos, Naghmeh Radhakrishna, Philip G. Bardin, Matthew Peters, Paul N. Reynolds, John W. Upham, Melissa Baraket, Simon Bowler, Jeffrey J. Bowden, Jimmy Chien, Li Ping Chung, Christopher Grainge, Christine Jenkins, Gregory Katsoulotos, Joy Lee, Vanessa M. McDonald, Helen K. Reddel, Janet Rimmer, Peter Wark, Peter G. Gibson
Abstract
Severe asthma is a high-burden disease. Real-world data on mepolizumab in patients with severe eosinophilic asthma is needed to assess whether the data from randomised controlled trials are applicable in a broader population. The Australian Mepolizumab Registry (AMR) was established with an aim to assess the use, effectiveness and safety of mepolizumab for severe eosinophilic asthma in Australia. Patients (n=309) with severe eosinophilic asthma (median age 60 years, 58% female) commenced mepolizumab. They had poor symptom control (median Asthma Control Questionnaire (ACQ)-5 score of 3.4), frequent exacerbations (median three courses of oral corticosteroids (OCS) in the previous 12 months), and 47% required daily OCS. Median baseline peripheral blood eosinophil level was 590 cells·µL −1 . Comorbidities were common: allergic rhinitis 63%, gastro-oesophageal reflux disease 52%, obesity 46%, nasal polyps 34%. Mepolizumab treatment reduced exacerbations requiring OCS compared with the previous year (annualised rate ratio 0.34 (95% CI 0.29–0.41); p<0.001) and hospitalisations (rate ratio 0.46 (95% CI 0.33–0.63); p<0.001). Treatment improved symptom control (median ACQ-5 reduced by 2.0 at 6 months), quality of life and lung function. Higher blood eosinophil levels (p=0.003) and later age of asthma onset (p=0.028) predicted a better ACQ-5 response to mepolizumab, whilst being male (p=0.031) or having body mass index ≥30 (p=0.043) predicted a lesser response. Super-responders (upper 25% of ACQ-5 responders, n=61, 24%) had a higher T2 disease burden and fewer comorbidities at baseline. Mepolizumab therapy effectively reduces the significant and long-standing disease burden faced by patients with severe eosinophilic asthma in a real-world setting.