A34-02 Dupilumab Discontinuation Leads to Worsening of Disease in Patients With Chronic Obstructive Pulmonary Disease: Pooled Data From Boreas and Notus

Abstract Rationale In BOREAS and NOTUS trials, dupilumab treatment for 52 weeks reduced exacerbations, improved lung function and quality of life (QoL), and reduced symptoms and fractional exhaled nitric oxide (FeNO) levels, in patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation. Following treatment discontinuation from Week 52 to Week 64, FeNO levels increased. This post hoc analysis of pooled data from BOREAS and NOTUS assessed the impact of treatment discontinuation on lung function and QoL. Methods BOREAS (NCT03930732) and NOTUS (NCT04456673), Phase 3, randomized, placebo-controlled trials, enrolled patients with COPD, moderate-to-severe airflow limitation, and type 2 inflammation (screening blood eosinophil count ≥300 cells/µL) on inhaled triple therapy. Patients received add-on dupilumab 300mg every 2 weeks or placebo for up to 52 weeks and entered a 12-week follow-up period of treatment discontinuation. Endpoints included serum dupilumab concentrations, pre- and post-bronchodilator forced expiratory volume in 1 second (FEV1), and St. George’s Respiratory Questionnaire (SGRQ) total scores (range: 0-100, lower scores indicating fewer symptoms and better QoL) at Weeks 52 and 64. Results This analysis included 1,660 patients (dupilumab: 830; placebo: 830) from the intention-to-treat population with an opportunity to reach Week 52. Following treatment discontinuation, the median (range) serum dupilumab concentrations decreased from 49,050 mg/mL (39-234,000) at Week 52 to 39 mg/mL (39-121,000) at Week 64. At Week 52, the mean (standard deviation SD) change from baseline in pre-bronchodilator FEV1 was 0.13 L (0.38) in dupilumab-treated patients and 0.05 L (0.33) in placebo-treated patients; by Week 64, these values declined to 0.07 L (0.35) and 0.03 L (0.32), respectively. Similar changes were observed for post-bronchodilator FEV1 (mean SD change from baseline in dupilumab-treated patients vs placebo-treated patients: at Week 52: 0.12 L 0.38 vs 0.04 L 0.32; at Week 64: 0.07 L 0.36 vs 0.03 L 0.33. Smaller reductions in SGRQ total score, indicating worsening of QoL, were observed at Week 64 in patients receiving dupilumab (mean SD change from baseline: −9.6 18.2 points) vs placebo (−6.0 16.8), compared to Week 52 (−6.8 17.9 points vs − 5.6 17.1). No new safety signals were observed between Weeks 52 and 64. Conclusions Discontinuing dupilumab treatment for 12 weeks led to worsening of lung function and QoL and reductions in dupilumab serum concentrations, accompanied by increased FeNO levels. These data suggest that continuous therapy is required to maintain treatment benefits for patients with COPD and underlying type 2 inflammation. This abstract is funded by: Sanofi and Regeneron Pharmaceuticals Inc.