Dupilumab Reduced COPD Exacerbations Compared to Placebo

Dupilumab add-on to standard triple therapy reduced the annualized moderate or severe exacerbations of chronic obstructive pulmonary disease (COPD) compared with placebo in a pooled analysis of phase 3 trial data.1

“Dupilumab is the first biologic that has consistently shown clinical efficacy and safety in patients with COPD with type 2 inflammation, indicated by elevated blood eosinophils. More research is needed to further assess the efficacy and safety of dupilumab in specific subgroups of people with COPD, including people of under-represented minoritized ethnicities and specific phenotypes of COPD,” lead investigator Surya P Bhatt, MD, professor, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama, and colleagues wrote.1

Bhatt and colleagues pooled and analyzed data from all patients in the intention-to-treat populations of the phase 3, randomized, double-blind, placebo-controlled BOREAS and NOTUS trials. These trials took place in other 200 hospitals each in 38 countries across Europe, Asia, North America, South America, Africa, and Australia. Participants were current or former smokers with 10 pack-years or more of smoking history aged 40–85 years with physician-diagnosed COPD for at least 12 months before randomization. They had to have post-bronchodilator FEV1/forced vital capacity (FVC) ratio of less than 0.7, post-bronchodilator percentage predicted FEV1 of 30–70%, documented evidence of 2 moderate or 1 severe exacerbations of COPD in the previous year (at least 1 exacerbation while on triple therapy), and blood eosinophil counts 300 cells per μL or more during screening. They also had to have symptomatic COPD and a reported chronic productive cough for at least 3 months in the previous year. Key exclusion criteria included history of asthma, other pulmonary disease, or other diagnosed pulmonary or systemic disease associated with elevated blood eosinophil. Both trials randomized participants to receive subcutaneous dupilumab 300 mg or matching placebo once every 2 weeks for 52 weeks alongside established background therapy with inhaled corticosteroids, a long-acting β2-agonist, and a long-acting muscarinic antagonist. Annualized rate of moderate or severe exacerbations over 52 weeks was the primary endpoint of both trials.

Altogether, 1874 patients were randomly assigned in BOREAS and NOTUS from May 2019 to May 2023 to dupilumab (n = 938; 50.1%) or placebo groups (n = 936; 49.9%). Most participants were male (66.8%), most were White (85.9%), and the mean age was 65.1 years (standard deviation, 8.2) across both groups. Most were former smokers (70.2%) and 38.4% were from Eastern Europe.1

The investigators found that 559 moderate or severe exacerbations were reported in 36.0% (n = 338) of the dupilumab group and 42.1% (n = 394) of the placebo group. The dupilumab group had a lower annualized exacerbation rate of 0.794 compared with 1.156 in the placebo group (incidence rate ratio [IRR], 0.687 [95% CI, 0.595–0.793]; P <.0001). The dupilumab group also had a longer time to first severe exacerbation than the placebo group (IRR, 0.611 [95% CI, 0.409–0.912]; P = .016). However, there was no significant reduction in the annualized rate of severe exacerbations (dupilumab, 0.084; placebo, 0.12; IRR, 0.674 [95% CI, 0.438–1.037]; P = .073). Safety between the 2 groups was comparable in terms of adverse events.1

Dupilumab was approved by the FDA as an add-on maintenance treatment of adults with inadequately controlled COPD under the name Dupixent in September 2024.2 It was the first biologic for this indication to be approved in the United States.

REFERENCES

1. Bhatt SP, Rabe KF, Hanania NA, et al. Dupilumab for chronic obstructive pulmonary disease with type 2 inflammation: a pooled analysis of two phase 3, randomised, double-blind, placebo-controlled trials. Lancet. Published online January 31, 2025. DOI: 10.1016/S2213-2600(24)00409-0

2. Press Release: Dupixent approved in the US as the first-ever biologic medicine for patients with COPD. News release. Sanofi. September 27, 2024. https://www.sanofi.com/en/media-room/press-releases/2024/2024-09-27-13-35-00-2954551