Dupilumab (Sanofi and Regeneron Pharmaceuticals, Inc.) enables patients with COPD and type 2 inflammation to avoid poor outcomes, according to results of a study of data from the BOREAS and NOTUS trials.
The BOREAS and NOTUS phase 3, double-blind, randomized controlled trials enrolled patients with COPD, moderate-to-severe airflow limitation, and type 2 inflammation while on triple therapy.
Adding dupilumab to the patients’ triple therapy increased their odds of avoiding death, hospitalization, exacerbations, worsening lung function, and worsening symptoms by 30% over 12 months.
To evaluate how add-on dupilumab affects clinical outcomes in these patients, the researchers conducted a win ratio analysis of pooled data from participants in the two trials.
The 1,872 participants were on triple therapy for COPD. They had moderate-to-severe airflow limitation and type 2 inflammation, defined as a baseline blood eosinophil count of at least 300 cells/μL. For 52 weeks, the 938 participants in the treatment group received subcutaneous dupilumab 300 mg every 2 weeks, while 934 participants received placebo.
The researchers used win-ratio analysis to compare each patient on dupilumab with each patient on placebo for the occurrence of specific events. Each compared pair had three possible outcomes at each endpoint: a dupilumab win, a tie, or a placebo win.
The endpoints, ranked by decreasing order of clinical importance, included avoiding: the hospital, moderate exacerbations, lung function loss, and symptom deterioration. The researchers compared the most important endpoints first and only compared the less important endpoints if the pair tied in all the preceding endpoints in the hierarchy of importance.
Patients in the dupilumab group were 30% more likely to avoid hierarchically important clinical deterioration compared to participants in the placebo group (win ratio 1.30; 95% CI, 1.15-1.46; P<0.0001).
Dupilumab was superior than placebo for death/hospitalization/emergency department visits of 24 hour or longer (7.6% vs 5.6%), moderate exacerbations or emergency department visits less than 24 hours (22.1% vs 17.9%), total moderate or severe exacerbations (3.8% vs 2.8%), a 10% or greater improvement in post-bronchodilator percent predicted forced expiratory volume in 1 second at Week 52 (ppFEV1 5.1% vs 3.1%).
The researchers also found a 2-point or greater improvement in Evaluating Respiratory Symptoms of COPD scores at Week 52 (7.6% vs 5.6%) and a 4-point or greater improvement in St. George’s Respiratory Questionnaire scores at Week 52 (2.3% vs 2.2%).
Similar results were seen when change in ppFEV 1 was replaced in the analysis with 100 mL or greater absolute FEV 1 improvement at Week 52 (7.0% vs 5.1%; win ratio 1.29 (95% CI, 1.15-1.45; P<0.0001). The net benefit was 0.11 (95% CI, 0.06-0.16; P<0.0001).
Reference
Ramakrishnan S, Couillard S, Petousi N, et al. Rapid Patient-Reported Symptom Improvement With Dupilumab in Patients With Chronic Obstructive Pulmonary Disease: Pooled Data From the BOREAS and NOTUS Trials. Presented at: CHEST 2025, October 19-22, 2025; Chicago.
