S31 Efficacy of dupilumab in chronic obstructive pulmonary disease with type 2 inflammation by baseline blood eosinophil count

Rationale Chronic obstructive pulmonary disease (COPD) is characterized by progressive lung function decline and worsening symptoms, accelerated by recurrent exacerbations. Type 2 (T2) inflammation may play a significant role in a subset of patients with COPD. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of T2 inflammation. Methods BOREAS (NCT03930732) was a 52-week, phase 3, placebo-controlled trial of the efficacy and safety of subcutaneous add-on dupilumab 300 mg q2w vs placebo in COPD patients with moderate-to-severe airflow limitation with T2 inflammation (blood eosinophils ≥300 cells/µL at screening) on triple therapy with inhaled corticosteroids (ICS), long-acting β2-agonists (LABA), and long-acting muscarinic antagonists (LAMA) (or LABA/LAMA if ICS was contraindicated). Primary endpoint: annualized rate of moderate or severe exacerbations (AECOPD). Secondary/other endpoints: change from baseline in pre-bronchodilator FEV1 at Weeks 12/52; change from baseline in St. George’s Respiratory Questionnaire (SGRQ) total score and E-RS: COPD RS-Total Score at Week 52; SGRQ responders with ≥4-point improvement from baseline at Week 52; blood eosinophil levels over time; and safety. Results 939 participants were randomized to placebo (N=471) or dupilumab (N=468). Treatment groups were balanced at baseline. Dupilumab met all multiplicity-adjusted endpoints. Dupilumab demonstrated a 30% reduction in the annualized rate of AECOPD (p=0.0005). In the entire study population, dupilumab vs placebo significantly increased pre-BD FEV1 at Week 12 (least squares mean (LSM) difference vs placebo: 83 mL, p<0.0001); through Week 52 (83 mL, p=0.0003). Dupilumab demonstrated greater improvement from baseline in pre-BD FEV1 at Week 52 in the subgroup of patients with baseline blood eosinophils ≥300 cells/µL (table 1). Median change from baseline in blood eosinophils was ‒30.00 cells/µL in both groups at Week 52. Safety was similar in the dupilumab and placebo groups. TEAEs were balanced between placebo and dupilumab groups. No clinically symptomatic eosinophilia was observed. Conclusions Dupilumab is the first biologic to significantly improve exacerbations, lung function, health-related quality-of-life, and symptoms in COPD patients with T2 inflammation. The dupilumab safety profile was consistent with other dupilumab indications. Please refer to page A283 for declarations of interest related to this abstract.