Dupilumab is associated with improved lung functions in patients with COPD and type 2 inflammation: a post hoc analysis of the BOREAS and NOTUS trials
MeiLan K Han, Klaus F Rabe, Frank C Sciurba, Claus F Vogelmeier, Surya P Bhatt, Antonio Anzueto, Mona Bafadhel, Stephanie A Christenson, Francesca Puggioni, Jinping Zheng, Alberto Papi, Dave Singh, Deborah Bauer, Mena Soliman, Jigna Heble, Nicola A HananiaAbstract
Rationale
Type 2 inflammation is present in 20%-40% of patients with chronic obstructive pulmonary disease (COPD).
Objective
To perform in-depth analyses of the efficacy of dupilumab on lung function parameters in patients with COPD and type 2 inflammation.
Methods
In BOREAS (NCT03930732) and NOTUS (NCT04456673), patients with COPD and type 2 inflammation were randomized to dupilumab 300 mg (n = 938) or placebo (n = 936) subcutaneously every 2 weeks for 52 weeks.
Measurements and main results
Dupilumab versus placebo improved pre-bronchodilator forced expiratory volume in 1 second (FEV1; least squares mean difference: 83 [95% confidence interval (CI): 53-112] mL; P < .0001), post-bronchodilator FEV1 (71 [41-101] mL; P < .0001), pre-bronchodilator forced vital capacity (FVC; 64 [26-102] mL; P = .0009), post-bronchodilator FVC (41 [3-79] mL; P = .0341), post-bronchodilator FEV1/FVC (0.016 [0.010-0.022]; P < .0001), and forced expiratory flow 25%-75% of FVC (78 [45-111] mL/s; P < .0001) at week 12 and sustained to week 52. Improvements in pre-bronchodilator FEV1 were observed regardless of smoking status or the presence of co-existing emphysema; greater improvements were observed in patients with higher baseline eosinophil counts or fractional exhaled nitric oxide. Dupilumab versus placebo achieved >100 mL improvements in pre-bronchodilator FEV1 at week 12 (42.2% vs 31.1%) and week 52 (36.9% vs 31.2%), with a similar proportion for post-bronchodilator FEV1 at weeks 12 and 52.
Conclusions
Dupilumab treatment resulted in early and sustained improvements across multiple spirometric lung function parameters in patients with COPD and type 2 inflammation.