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BackgroundMepolizumab, 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.MethodsWe 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.ResultsOf 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.ConclusionsPost-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.

IntroductionAdmission to hospital with a severe exacerbation of COPD (AECOPD) is associated with an increased risk of further exacerbations, readmission and death. Seasonality can affect exacerbation phenotype (Aung et al, 2024), but it remains unclear how season of onset affects ongoing risk following severe AECOPD.MethodsCOPD-HELP was a single-centre, double-blind, randomised, placebo-controlled trial that recruited 238 participants during hospitalisation for AECOPD and allocated them 1:1 to mepolizumab or placebo for 48 weeks. All participants had an eosinophil count ≥300 cells/µL on at least one occasion in the prior 12 months, were established on inhaled corticosteroids and current or ex-smokers. Full details are published elsewhere. (Flynn et al., 2025)For this analysis, 119 participants on placebo were included. Exacerbation rates were analysed based on an individual’s season of entry into the trial.. Entry into trial occurred within a week of a severe AECOPD for all participants. Exacerbation rates were calculated as the total number of exacerbations per participant, offset by time in trial. A linear regression model was fitted, using season of study enrolment as the primary predictor variable and exacerbation rate in the preceding 12 months as a covariateResultsAdjusted annual exacerbation rates varied significantly by season, with the highest rate in summer (adjusted mean 5.76, 95% CI, 5.33 – 6.19), followed by autumn (4.02, 95% CI, 3.47 – 4.57), spring (3.98, 95% CI, 3.28 – 4.69), and lowest in winter (3.48, 95% CI, 2.92 – 4.04). This represents a relative increase of 65% following an exacerbation in summer compared to winter.Abstract P13 Figure 1[Image Omitted. See PDF.]ConclusionsIn an eosinophilic COPD population, severe exacerbations in summer were associated with a higher rate of exacerbations in the following year than those in any other season. This group may be particularly susceptible to environmental exposures such as increased pollen levels, pollution index or other seasonal allergens. Greater understanding of seasonal dynamics and mechanisms driving recurrent exacerbations could play a role in risk reduction and post exacerbation care and guidance.