Dupilumab Cuts COPD Exacerbations Across Seasons, Smoking Status: Surya Bhatt, MD

Dupilumab is approved for chronic obstructive pulmonary disease (COPD) with chronic bronchitis and type 2 inflammation, defined by blood eosinophil counts of 300 cells/µL or higher, in patients remaining uncontrolled on triple therapy. GOLD 2026, published just ahead of European Respiratory Society (ERS) International Congress, held in Barcelona from September 5-9, added mepolizumab alongside dupilumab as a second biologic option for this same eosinophilic, exacerbation-prone phenotype.

A post hoc analysis of pooled BOREAS and NOTUS data assessed dupilumab versus placebo across all 4 seasons by exacerbation start date, since winter exacerbations are disproportionately infection-driven while type 2 inflammatory exacerbations are not. Dupilumab reduced exacerbation rates by 25.9% in winter, 33.4% in spring, 33.1% in summer, and 27.1% in fall (all P≤.005).1 Events requiring both systemic corticosteroids and antibiotics, the most resource-intensive category, were numerically lower with dupilumab in every season.

A separate pooled analysis stratified by smoking status found dupilumab reduced exacerbation rates by 32% in both current and former smokers, with a non-significant treatment-by-subgroup interaction (P = .85).2 Current smokers are often excluded from or underrepresented in COPD biologic trials, and dupilumab carries no smoking cessation prerequisite for initiation.

Across the METREX, METREO, and MATINEE trials, mepolizumab reduced exacerbations by 18% to 21% without significant gains in lung function or quality of life, while dupilumab improved both alongside exacerbation reduction of 30% to 34% in its pivotal trials.3 Both analyses discussed here are post hoc rather than prespecified, so clinicians should weigh them as supportive context within approved labeling rather than as new indications.

Surya Bhatt, MD, MSPH, professor of medicine in the Division of Pulmonary, Allergy, and Critical Care Medicine at the University of Alabama at Birmingham, discussed these findings with HCPLive at the ERS Congress 2026 in Barcelona. In the following interview, Bhatt addresses what the seasonal and smoking status data add to choosing between dupilumab and mepolizumab in COPD.

HCPLive: What was the hypothesis behind this seasonal analysis, and what does the consistent exacerbation reduction across seasons suggest about dupilumab's mechanism?

Surya Bhatt, MD, MSPH: The goal of this analysis was to understand how dupilumab performs across seasons regardless of the presence of specific exacerbation triggers within a particular season. Given type 2 inflammation doesn't drive exacerbations only in response to specific triggers, we expected dupilumab to work similarly across seasons. Therefore, the results are consistent with our expectations, demonstrating that, regardless of season, dupilumab consistently and significantly reduced exacerbations.

HCPLive: Why is the reduction in exacerbations requiring both steroids and antibiotics particularly meaningful for frequent exacerbators?

Surya Bhatt, MD, MSPH: The decision to treat a particular patient with steroids alone, antibiotics alone, or with both is a clinical decision often made by clinicians based on clinical gestalt and prior response to these medications. Although individual events were not phenotyped for etiology, the broad efficacy of dupilumab for all types of events raises confidence that the efficacy is not confined to steroid-responsive type 2 inflammation-related exacerbations only.

HCPLive: Should smoking cessation remain a prerequisite before initiating dupilumab in a patient who meets the eosinophil threshold?

Surya Bhatt, MD, MSPH: Dupilumab is already approved for eligible patients with COPD, including both current and former smokers, so smoking cessation is not a requirement to initiate dupilumab. This analysis confirms that dupilumab not only significantly reduces exacerbations in current or former smokers, but also led to improvements in other key outcomes in both populations, including improvements in lung function, health-related quality of life, and reduction in symptom burden compared to placebo.

HCPLive: How should clinicians weigh post hoc subgroup findings when making treatment decisions for dupilumab in COPD?

Surya Bhatt, MD, MSPH: Clinicians should continue to prescribe dupilumab in accordance with local regulatory guidelines in alignment with approved labeling. However, post hoc analyses like these provide additional information on the potential outcomes across patient populations or other specific variables when prescribing dupilumab. These two post hoc analyses, for example, can provide clinicians more confidence in administering dupilumab regardless of smoking status and across seasons.

HCPLive: With 2 biologics now in the GOLD algorithm, how should clinicians choose between dupilumab and mepolizumab for individual patients?

Surya Bhatt, MD, MSPH: Dupilumab is currently the only approved biologic for COPD that has demonstrated improved outcomes across exacerbations, lung function, and health-related quality of life. Dupilumab is already approved for eligible patients regardless of smoking status and can be used in any season, but the results from these post hoc analyses provide additional data that could give healthcare providers a more holistic understanding of the outcomes their patients might see while on dupilumab.

Editor's Note: This transcript has been edited for grammar and clarity using artificial intelligence tools. Bhatt’s disclosures include Sanofi, Regeneron, Apreo, Boehringer Ingelheim, GSK, Genentech, Merck, and others.

References

1. Criner G, Wilkinson T, Sciurba F, et al. Dupilumab reduces exacerbations regardless of season in patients with chronic obstructive pulmonary disease. Presented at: ERS Congress 2026; September 5-9, 2026; Barcelona, Spain.

2. Bhatt S, et al. Dupilumab is efficacious in chronic obstructive pulmonary disease with type 2 inflammation regardless of smoking status. Presented at: ERS Congress 2026; September 5-9, 2026; Barcelona, Spain. Abstract PA2555.

3. Cazzola M, Bajpai J, Calzetta L, Matera MG, Rogliani P. GOLD 2026: transforming COPD management with early intervention, multi-dimensional assessment, and personalized care. Drugs. 2026;86(5):581-597. doi:10.1007/s40265-026-02303-3