Efficacy and Safety of Dupilumab for COPD with Type 2 Inflammation Indicated by Elevated Eosinophils

Introduction: Dupilumab (DPL), a fully human mAb, blocks the shared receptor component for IL-4 and IL-13, key/central drivers of Type 2 (T2) inflammation.

Objective: Determine efficacy/safety in patients with moderate-to-severe COPD with T2 inflammation.

Methods: BOREAS (NCT03930732) was a 52-week (wk), phase 3, randomized, double-blind, placebo (PBO)-controlled trial of efficacy/safety of biweekly DPL 300mg in COPD pts with blood eosinophils ?300cells/µL at screening, on triple therapy (an inhaled corticosteroid [ICS], long-acting ?2-agonists [LABA], and long-acting muscarinic antagonists [LAMA]; or LABA/LAMA if ICS was contraindicated) without asthma diagnosis/history. Primary endpoint: annualized rate of moderate-severe exacerbations. Secondary/other endpoints: change from baseline (BL) in pre-bronchodilator FEV1 at wk 12 and wk 52; cumulative exacerbations over time; safety.

Results: 939 participants were randomized to PBO (N=471) or DPL (N=468). DPL reduced exacerbation rates by 30% vs PBO (p=0.0005). DPL significantly increased pre-BD FEV1 at wk 12 (LSM difference vs PBO: 83mL, p<0.0001); sustained through wk 52 (83mL, p=0.0003). This trended towards reduced exacerbation-associated annualized total SCS treatment duration for DPL (13.57 days [SD 13.17] vs for PBO (19.09 days [SD 20.65]). Safety similar in DPL and PBO groups; TEAEs balanced.

Conclusions: DPL significantly improved moderate-severe exacerbations, lung function, quality of life, and symptoms in COPD patients with T2 inflammation. The use of SCS days required for the treatment of AECOPD trended lower with DPL.