S176 A subgroup analysis of COPD-HELP – mepolizumab for COPD with eosinophilic phenotype following hospitalisation – stratified by eosinophil levels

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Background Mepolizumab, a monoclonal antibody to interleukin-5, has been shown to reduce exacerbations (Sciurba, NEJM 2025) in people with chronic obstructive pulmonary disease (COPD) and increased blood eosinophils in the past year, but did not improve time to readmission or death following hospitalisation (Flynn, NEJM Evidence 2025). We hypothesised that eosinophil count at index admission and functional capacity influence the effect of mepolizumab in this hospitalised population. Methods We performed post-hoc analyses on data from COPD-HELP, a double-blind, placebo-controlled, randomised trial where 238 patients hospitalised with AECOPD and evidence of eosinophilic phenotype (blood eosinophil count ≥300 cells/µL at least once in prior year) were randomised to mepolizumab 100 mg or placebo for 48 weeks. All participants had extended MRC dyspnoea score (eMRC [range: 1–5b]) ≥2, were on inhaled corticosteroids and had significant smoking history. Primary outcome was time to rehospitalisation or death. Cox proportional hazards models were fitted for the overall population and the subgroup with eMRC 2–4 (n=184), including treatment group, eosinophil group at admission (‘low’ <300 cells/µL or ‘high’ ≥300 cells/µL) and their interaction. Results Of 238 participants, 119 were allocated mepolizumab (54 [45%] eosinophilic at admission) and 119 placebo (65 [55%] eosinophilic). In those with a ‘high’ blood eosinophil count mepolizumab was associated with a hazard ratio (HR) of 0.69 (95% CI 0.44 to 1.09) compared to placebo. In contrast, for those with a ‘low’ blood eosinophil count the mepolizumab versus placebo HR was 1.3 (0.82 to 2.05). In those with eMRC 2–4 and a ‘high’ blood eosinophil count at admission, the HR for mepolizumab versus placebo was 0.61 (95% CI 0.36 to 1.03; n=99). In those with ‘low’ blood eosinophils at admission and eMRC 2–4 the HR was 1.47 ( 95% CI 0.86 to 2.52; n=85). The hazard ratio for the eosinophil group-by-treatment interaction was 0.53 (95% CI 0.28 to 1.01; p=0.053) in the overall population and 0.41 (0.19 to 0.86; p=0.019) in the eMRC 2–4 subgroup. Conclusions Post-hoc analyses of COPD-HELP suggest that mepolizumab initiated at severe exacerbation conveys greater benefit in those with evidence of eosinophilic inflammation at admission, particularly in combination with better functional status.

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