Mepolizumab Cuts COPD Exacerbations Across Smoking Status: Claus Vogelmeier, MD

Which data support mepolizumab’s benefit?

A pooled analysis of the phase 3 METREX, METREO, and MATINEE trials found that mepolizumab (GSK) reduced moderate or severe exacerbations in patients with eosinophilic chronic obstructive pulmonary disease (COPD) regardless of whether they were current or former smokers, though the drug's benefit on more serious outcomes appeared limited to former smokers, according to Claus F. Vogelmeier, MD, professor of medicine and head of the Department of Medicine, Pulmonary and Critical Care Medicine at the University Medical Center Giessen and Marburg. Vogelmeier discussed the pooled analysis, presented at the 2026 European Respiratory Society (ERS) Congress, held September 5 to 9 in Barcelona, Spain, in an interview with HCPLive.

The analysis stratified patients by smoking status and by blood eosinophil count (BEC) at screening (≥150 cells/µL or ≥300 cells/µL). Mepolizumab significantly reduced annualized moderate/severe exacerbations versus placebo in former smokers by 19% (BEC ≥150 cells/µL) and 25% (BEC ≥300 cells/µL), and in current smokers by 23% (BEC ≥150 cells/µL) and 18% (BEC ≥300 cells/µL, not statistically significant).¹ Former smokers also had significant reductions in exacerbations requiring emergency department visits or hospitalization and in severe exacerbations, while current smokers did not show significant reductions on either of those more serious outcomes.¹ Vogelmeier said this split reflects a real and clinically relevant distinction, but not one that should keep clinicians from treating active smokers who continue to exacerbate.

How should these data inform treatment decisions?

"You have an active smoker that maybe has a history of severe exacerbations. You may start with the drug right away, although he's still actively smoking, but then you should try everything to get him away from the cigarettes," he said.

Mepolizumab is now the second biologic approved for COPD after dupilumab, and while comparable smoking-status data exist for dupilumab, Vogelmeier said the pooled nature of this analysis is itself a strength: because METREX, METREO, and MATINEE had somewhat heterogeneous inclusion criteria, combining them produced a broader, more clinically representative population than any single randomized trial typically captures. He said the data do not change his approach to initiating treatment in active smokers with a history of exacerbations, since the primary endpoint signal held even in that group, but they do reinforce that the expected effect size on the most serious outcomes is smaller until a patient stops smoking. GSK funded the trials.¹

Vogelmeier’s disclosures include AstraZeneca, CSL Behring, GSK, Hoffman – La Roche, Insmed, Sanofi, Boehringer Ingelheim, Novartis, and more.

References

1. Vogelmeier C, Wald J, Anzueto A, et al. Mepolizumab reduces moderate or severe exacerbations in patients with COPD irrespective of baseline smoking status: pooled Phase III trial results. Presented at: European Respiratory Society (ERS) Congress 2026; September 5-9, 2026; Barcelona, Spain.

2. Sciurba FC, Criner GJ, Christenson SA, et al. Mepolizumab to prevent exacerbations of COPD with an eosinophilic phenotype. N Engl J Med. 2025;392(17):1710-1720. doi:10.1056/NEJMoa2413181