A34-27 Dupilumab Improves BODE Index and Dyspnea Scores in Patients With Chronic Obstructive Pulmonary Disease and Type 2 Inflammation: A Post Hoc Analysis From NOTUS

Abstract Rationale The BODE index is a multidimensional tool used to predict mortality risk in patients with chronic obstructive pulmonary disease (COPD). The tool comprises several interrelated, but distinct, domains: body mass index (B), airflow obstruction (O), dyspnea (D), and exercise capacity (E), each independently associated with increased mortality. The progressive and systemic nature of COPD means that significant improvements in BODE index scores are difficult to achieve for most patients. Dyspnea, one of the main symptoms experienced by patients with COPD, is a key component of the BODE index. Achieving scores of 0 or 1 on the modified Medical Research Council (mMRC) scale is challenging for patients with moderate or severe COPD, who typically present with mMRC scores ≥2. In phase 3 BOREAS and NOTUS, add-on dupilumab vs. placebo significantly reduced moderate or severe exacerbation rates and improved lung function, quality of life, and symptoms in patients with COPD and type 2 inflammation. This post hoc analysis of NOTUS evaluated the effect of dupilumab on the BODE index score, as well as the dyspnea component score. Methods NOTUS (NCT04456673), a phase 3, randomized, placebo-controlled trial, enrolled patients with COPD, moderate-to-severe airflow limitation, and type 2 inflammation (screening blood eosinophils ≥300 cells/µL) on inhaled triple therapy. Patients were randomized to receive dupilumab 300 mg or placebo every 2 weeks. We assessed the BODE index score (range: 0-10; lower scores indicating less disease severity and reduced mortality risk) and the dyspnea component score (mMRC scale; range: 0-4; lower scores indicating less dyspnea) in the intention-to-treat population. Symptom burden scores were classified as low for dyspnea scores ≤1 and high for scores ≥2. Results This analysis included 935 patients (dupilumab: N = 470; placebo: N = 465). At baseline, the BODE index score and the distribution of mMRC dyspnea scores were similar between treatment arms. The change from baseline to Week 52 (mean standard deviation) in the overall BODE index score for dupilumab vs. placebo was −0.6 (1.5) vs. −0.3 (1.5) points (Table). Overall, there was a trend towards lower mMRC scores at Week 52 compared with the baseline distribution, where a higher proportion of patients receiving dupilumab (13.1%) achieved mMRC scores of ≤ 1 than those on placebo (9.2%) (Table). Conclusions In patients with COPD and type 2 inflammation, treatment with dupilumab was associated with a greater reduction in the BODE index score and improvements in dyspnea burden at Week 52. This abstract is funded by: Sanofi and Regeneron Pharmaceuticals Inc. ClinicalTrials.gov Identifier: NCT04456673