Severe asthma outcomes over 18-months treatment with mepolizumab, and comorbidities in non-responders

Introduction: Mepolizumab is an anti-IL-5 monoclonal antibody indicated for the treatment of severe asthma. We have evaluated patient outcomes over the first 18-months of treatment, and investigated comorbidities in non-responders. Method: Data from 120 patients were analysed. Patients stopping within 12 months underwent further clinical assessment. Results: 86(72%) of patients responded, achieving a 50% reduction in daily prednisolone dose and/or annual exacerbation rate. 20 stopped due to non-response, five due to side effects and eight due to patient choice. In responders, 12-month improvements in prednisolone use, exacerbation rate, asthma quality of life questionnaire(AQLQ) and asthma control questionnaire(ACQ) were maintained at 18-months(table1). Non-responders had lower median (IQR) baseline blood eosinophils than responders [0.07(0.02-0.24)vs 0.17(0.05-0.32),p = 0.048], and a 12-month rise in mean (SD) FeNO [35(33)to50(20)ppb,p = 0.012]. Significant comorbidity was present in 62%(n=28) of patients stopping treatment [tracheomalacia(31%), bronchiectasis(21%), inducible laryngeal obstruction(13%), breathing pattern disorder(27%), combination(21%)]. Conclusion: 12-month benefit from mepolizumab is maintained at 18 months. Treatment-failures may have a phenotype driven more by the IL4/IL13 pathway. Over half of the patients who failed to respond or stopped treatment had significant respiratory comorbidity.