COPD-HELP: A Randomised Controlled Trial of Mepolizumab Initiated Following Admission to Hospital for a Severe Exacerbation of Eosinophilic COPD

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Abstract Rationale Admission to hospital with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with a high risk of readmission and death. A proportion of patients with COPD have type 2 inflammation, as indicated by raised blood eosinophil count, for which targeted biologic treatment has been shown to reduce moderate, community-treated exacerbations. Mepolizumab is a monoclonal antibody to interleukin-5 which effectively reduces eosinophilic inflammation, but effects on future hospitalisations and mortality in COPD are uncertain. Methods COPD-HELP was a single-centre, phase IIb, double-blind, placebo-controlled study that randomised patients who were admitted to hospital with an acute exacerbation of COPD to either mepolizumab 100mg or placebo every 4 weeks for 48 weeks. All participants (≥40 years) had a blood eosinophil count of at least 300 cells per microlitre in the 12 months prior to admission, were established on inhaled corticosteroids at time of admission and alternative diagnoses or causes of eosinophilia were excluded. The primary end point was the time to readmission or death due to any cause. Key secondary endpoints included number of hospital readmissions, number of moderate or severe exacerbations, and health related quality of life. Results A total of 238 patients were randomised (119 in each group). The median time to rehospitalisation or death (all cause) was 25.4 weeks in the mepolizumab arm and 26.1 weeks in the placebo arm, with Kaplan-Meier estimates of 33.9% and 31.0% respectively (HR 0.96 (95%CI 0.7 to 1.32, p=0.811). The adjusted mean (95% CI) number of hospital readmissions over 48 weeks was 1.65 (1.25 to 2.05) with mepolizumab and 1.85 (1.42 to 2.29) with placebo (rate ratio [95% CI] 0.89 [0.64 to 1.25]). The adjusted mean (95% CI) number of moderate or severe exacerbations over 48 weeks was 2.80 (2.36 to 3.23) with mepolizumab and 3.45 (2.94 to 3.95) with placebo (rate ratio [95% CI] 0.81 [95% CI 0.66 to 1.00]). Conclusion Patients hospitalised with an acute exacerbation of COPD and evidence of eosinophilic inflammation had no benefit in risk of severe exacerbations or death when given mepolizumab for 48 weeks. A numerical reduction in the number of exacerbations was observed, consistent with previous trials.

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