Mepolizumab Reduces Type 2 COPD Exacerbations Across Variable BEC Levels

An exploratory pooled analysis of the Phase 3 METREX, METREO, and MATINEE trials has demonstrated that mepolizumab (Nucala; GSK) consistently reduced the annualized rate of moderate or severe exacerbations in people with chronic obstructive pulmonary disease (COPD) compared with placebo, regardless of blood eosinophil count (BEC) variability pattern.1

Mepolizumab was approved by the United States (US) Food and Drug Administration (FDA) in May 2025 as an add-on maintenance treatment for patients with COPD with an eosinophilic phenotype.2 BECs are an established biomarker of type 2 inflammation in COPD and are associated with increased exacerbation risk. Yet BEC levels are dynamic, influenced by infections, corticosteroid exposure, circadian variation, and other factors. Real-world data suggest that only 5–18% of patients demonstrate persistently high BEC ≥300 cells/µL, while nearly 30% exhibit intermittent elevations. This variability complicates clinical decision-making and raises important questions about how to identify patients most likely to benefit from biologic therapy.1

The analysis, presented by Gerald Criner, MD, Chair and Professor of Thoracic Medicine and Surgery at Lewis Katz School of Medicine at Temple University, at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2026 Annual Meeting held in Philadelphia, Pennsylvania, valuated mepolizumab 100 mg subcutaneously versus placebo in patients ≥40 years of age with COPD receiving inhaled triple therapy. Patients were stratified by longitudinal pre-randomization BEC patterns to assess whether variability in eosinophil levels influences response.1

Criner and colleaguges found that across patients with evidence of type 2 inflammation, mepolizumab consistently reduced the annualized rate of moderate or severe exacerbations compared with placebo, regardless of BEC variability pattern.

In Subgroup 1 (BEC ≥300 cells/µL at screening and baseline), exacerbation rates were reduced from 1.31 events/year with placebo to 0.95 with mepolizumab (rate ratio [RR], 0.73; 95% CI 0.61–0.88), corresponding to a 27% relative risk reduction.1

Subgroup 2 (persistently ≥300 cells/µL across all pre-randomization timepoints) showed a numerical reduction from 1.11 to 0.97 events/year (RR, 0.88; 95% CI 0.70–1.11), equating to a 12% relative risk reduction.1

Subgroup 3, (high type 2 inflammation at screening [≥300 cells/µL] but short-term variability [<300 cells/µL at baseline]), experienced a decrease from 1.27 to 0.99 events/year (RR, 0.78; 95% CI 0.60–1.01), representing a 22% relative risk reduction.1

Notably, Subgroup 4 (≥300 cells/µL at any pre-randomization timepoint with at least one measurement <150 cells/µL) demonstrated one of the largest treatment effects. Exacerbation rates declined from 1.43 to 0.91 events/year (RR, 0.64; 95% CI 0.45–0.89), corresponding to a 36% relative risk reduction. This subgroup also had among the highest placebo exacerbation rates, suggesting that patients with marked BEC variability may represent a particularly high-risk and responsive phenotype.1

Patients meeting the US-approved eosinophilic phenotype definition (Subgroup 5: ≥150 cells/µL at screening and/or ≥300 cells/µL in the prior year) experienced a reduction from 1.36 to 1.10 events/year (RR, 0.81; 95% CI 0.72–0.91), a 19% relative risk reduction. Similar significant reductions were observed in Subgroup 6 (RR, 0.83; 17% risk reduction) and Subgroup 7 (RR, 0.79; 21% risk reduction).1

In contrast, Subgroup 8 of non-type 2 COPD (persistently <150 cells/µL) showed no meaningful benefit; rates increased from 1.17 to 1.47 events/year (RR, 1.26; 95% CI 0.98–1.61), indicating no protective effect in the absence of type 2 inflammation.1

For exacerbations requiring emergency department (ED) visit and/or hospitalization, results generally mirrored the moderate/severe findings, with efficacy across BEC levels except in Subgroup 8 in those without type 2 COPD Again, no meaningful benefit was observed (RR, 1.11; 95% CI 0.63–1.97).1

Subgroup 3 demonstrated the largest relative reduction in severe outcomes, with rates decreasing from 0.27 to 0.12 events/year (RR, 0.44; 95% CI 0.25–0.80), representing a 56% relative risk reduction.1

Subgroup 5 showed a reduction from 0.26 to 0.20 events/year (RR, 0.77; 95% CI 0.60–0.99), corresponding to a 23% relative risk reduction. Subgroups 6 and 7 demonstrated consistent directional improvements (RR, 0.77 and 0.76, reflecting 23% and 24% relative risk reductions, respectively).1

Overall, this analysis supports the use of mepolizumab in patients with inadequately controlled COPD and documented type 2 inflammatory activity, consistent with its US-approved indication, and suggests that requiring persistent eosinophilia may unnecessarily exclude patients who could achieve meaningful risk reduction.

“Mepolizumab consistently reduces exacerbation rates in a wide spectrum of patients with COPD and type 2 inflammation versus placebo, both in those who have high and low variability in their BECsover time, as well as those with historically elevated BEC, prior to therapy initiation. These results support the use of mepolizumab in patients who have shown signsof type 2 inflammation, without necessarily being persistently eosinophilic,” Criner and colleagues wrote in their poster.1

References

1. Criner GJ, Watz H, Han MK, et al. MepolizumabImproves Exacerbation Outcomes in Patients with COPD with Type 2 Inflammation and Variable Eosinophil Patterns. Presented at: AAAAI 2026 Annual Meeting, February 27-March 2, Philadelphia, Pennsylvania. Poster #L01.

2. Johnson V. FDA Approves Mepolizumab for Eosinophilic COPD. Article. HCPLive. May 22, 2025. https://www.hcplive.com/view/fda-approves-mepolizumab-for-eosinophilic-copd