Treatment with dupilumab significantly improved lung function and quality of life and reduced symptom burden and exacerbations in adults with chronic obstructive pulmonary disease (COPD) regardless of current or former smoking habit, based on new data from a pooled analysis of two phase 3 studies.

“Smoking is not only a key risk factor for COPD, but it can also impact the efficacy of other COPD medicines, such as inhaled corticosteroids. So it is important to understand how dupilumab performs, not only in former smokers but also in those who continue to smoke,” said lead author Surya P. Bhatt, MD, professor of medicine at the University of Alabama in Birmingham.

Dupilumab was approved by the FDA in 2024 for eligible patients with COPD, regardless of smoking status. The new analysis provides further confidence that dupilumab can improve multiple COPD measures in either population.

Bhatt and colleagues reviewed data from two randomized, double-blind, placebo-controlled phase 3 trials, BOREAS and NOTUS. Participants were stratified into groups of current smokers and former smokers. Exacerbation rates were reduced by 32% in patients in either group who received dupilumab compared to placebo after 52 weeks (P for interaction = .85).

Quality of life scores also improved significantly in both former and current smokers treated with dupilumab vs placebo, with changes in scores on the St. George’s Respiratory Questionnaire of -10.1 and -9.0, respectively, compared with changes of -6.3 and -6.6, respectively, in the placebo patients (P for interaction = .46).

In addition, dupilumab significantly improved lung function compared to placebo in current and former smokers, based on both pre- and postbronchodilator forced expiratory volume in 1 second at both 12 weeks and 52 weeks.

The results aligned with the researchers’ expectations based on the phase 3 trials, which showed that dupilumab significantly improves outcomes in a combined population of current and former smokers, said Bhatt. Looking ahead, further studies could evaluate additional subgroups of interest, he noted.

Value of Real-World Data

“Smoking remains the leading driver of COPD progression, and current smokers often have worse outcomes and reduced response to standard anti-inflammatory therapies, particularly inhaled corticosteroids,” said Jamie Garfield, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia.

Given that a substantial proportion of patients with COPD and type 2 inflammation continue to smoke, knowing whether dupilumab’s benefits extend to this real-world subgroup is useful for clinical practice, said Garfield, who was not involved in the study.

The findings were reassuring, though not entirely surprising, said Garfield. “Given prior evidence that active smoking can blunt responses to inhaled corticosteroids, one could have expected less benefit in current smokers; however, dupilumab targets type 2 inflammatory signaling through a pathway distinct from corticosteroids, so preservation of benefit across smoking groups is clinically plausible,” she said.

“Some outcomes appeared numerically less robust in current smokers, which keeps the results from being definitive,” Garfield noted. In addition, smoking status was self-reported, and the analysis did not fully account for smoking intensity, duration, biochemical confirmation, or changes in smoking behavior during treatment, she said. Additional prospective studies should evaluate dupilumab response by smoking burden, verified cessation status, and longer-term outcomes such as lung-function decline, Garfield said.

Despite these limitations, “active smoking alone should not automatically exclude an otherwise appropriate patient with eosinophilic COPD from consideration for dupilumab, particularly if they remain symptomatic or exacerbation-prone despite optimized triple inhaled therapy,” said Garfield.

The current study findings suggest that reductions in exacerbations and improvements in lung function, symptoms, and quality of life are maintained regardless of baseline smoking status, she added. “Importantly, dupilumab should complement — not replace — aggressive tobacco treatment, since smoking cessation remains the most important disease-modifying intervention in COPD,” Garfield emphasized.

The study was supported by Sanofi and Regeneron Pharmaceuticals.

Bhatt disclosed serving as a consultant or advisory board member for Aerogen, Apreo, AstraZeneca, Chiesi, Connect Biopharma, Genentech, GSK, Kymera, Merck, Polarean, Prana Therapies, Sanofi, Regeneron, Uniquity, Verona Pharma, and Zymeworks. He also disclosed honoraria for CME from Horizon CME, Illuminate Health, Integritas Communications, IntegrityCE, and Medscape, and serves on the Science Committee of the Global Initiative for Chronic Obstructive Lung Disease. Bhatt’s institute has received research funds from Apreo, Connect Biopharma, COPD Foundation, Genentech, Nuvaira, Sanofi, and Uniquity.

Garfield had no financial conflicts to disclose.