A34-23 Dupilumab Improves Outcomes Across a Larger Group of Study Population - Investigating Patient-Level Data

Abstract Rationale Analysis of patient-level data can provide additional insights into efficacy findings from clinical trials, avoiding the potential for a small number of patients to skew the results of the general study population. In BOREAS and NOTUS, add-on dupilumab significantly reduced moderate or severe exacerbation rates and improved lung function, symptom control, and quality of life in patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation. This post hoc analysis of pooled data from BOREAS and NOTUS used patient-level data to further evaluate the impact of dupilumab on exacerbations and lung function in patients with COPD and type 2 inflammation. Methods BOREAS (NCT03930732) and NOTUS (NCT04456673), phase 3, randomized, placebo-controlled trials, enrolled patients aged 40 to 85 years with physician-diagnosed COPD, moderate-to-severe airflow limitation, and type 2 inflammation (screening blood eosinophil count ≥300 cells/µL) on background inhaled triple therapy. Patients were randomized to either dupilumab 300 mg or placebo every 2 weeks for 52 weeks. Endpoints assessed were number of moderate or severe exacerbations during BOREAS and NOTUS and mean change from baseline to Week 52 in post-bronchodilator forced expiratory volume in 1 second (FEV1) and post-bronchodilator forced vital capacity (FVC). Results This analysis included 938 patients who received dupilumab and 936 who received placebo. The number of exacerbations in the year before enrollment was similar between dupilumab and placebo treatment arms. During the study, the number of exacerbations was lower in patients receiving dupilumab compared with those receiving placebo (Figure 1A). Inflection points, representing the proportion of patients with a positive response vs those with a negative response, were higher in patients receiving dupilumab vs placebo for Week 52 change from baseline in post-bronchodilator FEV1 (Figure 1B). Similar results were observed in FVC between dupilumab and placebo treatment arms (Figure 1C). For FEV1 and FVC, the curves showed a uniform concave distribution for both treatment arms, indicating that findings were not driven by large responses in a small number of patients. Conclusion Dupilumab treatment reduced the number of moderate or severe exacerbations and improved the proportion of patients with a positive response in lung function change in patients with COPD and type 2 inflammation, compared with placebo. Our findings show that overall results from the study populations were not driven by a small number of super-responders. This abstract is funded by: Sanofi and Regeneron Pharmaceuticals Inc. ClinicalTrials.gov Identifiers: NCT03930732 and NCT04456673