(239) Dupilumab efficacy in patients with Chronic Obstructive Pulmonary Disease (COPD) and Type 2 Inflammation with and without Emphysema

Background: : In chronic obstructive pulmonary disease (COPD, the presence of different pathobiological subtypes of airway disease (with symptoms of chronic bronchitis) and emphysema contributes to the complexity of the disease and its management. In the phase 3 BOREAS and NOTUS trials, add-on dupilumab vs placebo significantly reduced the rate of moderate or severe exacerbations and improved lung function in patients with COPD and type 2 inflammation; safety was consistent with the known dupilumab safety profile.

Objective: : To evaluate the efficacy of dupilumab in patients with COPD and type 2 inflammation with or without investigator-reported emphysema, based on pooled data from BOREAS and NOTUS trials.

Methods: : BOREAS (NCT03930732) and NOTUS (NCT04456673), both phase 3, randomized, placebo-controlled trials, enrolled 1,874 patients (aged 40 to 85 years) with COPD, moderate-to-severe airflow limitation, and type 2 inflammation (blood eosinophil count ≥300 cells/L at screening). Patients were randomized to either dupilumab (n=938) 300 mg or placebo (n=936) every 2 weeks subcutaneously for 52 weeks. Endpoints assessed included annualized moderate or severe exacerbation rates and change from baseline to Week 12 in pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV1) in patients with or without emphysema.

Results: : Of 1,874 patients, 590 (31.5%) had emphysema (dupilumab n=289; placebo n=301). Baseline characteristics were similar across the subgroups and treatment arms. Over the 52-week treatment period, dupilumab reduced annualized moderate or severe exacerbation rates by 34% (relative risk vs placebo [95% CI]: 0.66 [0.53, 0.82]) in patients with emphysema and by 30% (0.70 [0.58, 0.85]) in those without. Dupilumab improved pre-BD FEV1 to a similar magnitude in both subgroups (least squares mean difference vs placebo [95% CI] in patients with emphysema: 83 [35, 131] mL, and those without: 83 [45, 120] mL). No treatment by emphysema interaction effect was observed for the annualized exacerbation rates (P value=0.658) or change in pre-BD FEV1 (P value=0.999).

Conclusions: : Approximately one-third of patients participating in BOREAS and NOTUS had investigator-reported emphysema. Dupilumab reduced moderate or severe exacerbation rates and improved lung function in patients with COPD and type 2 inflammation, irrespective of the presence of emphysema.

Sponsorship:: Sanofi and Regeneron Pharmaceuticals, Inc.