Association between dupilumab and repeated exacerbations of chronic obstructive pulmonary disease: BOREAS and NOTUS

<bold>Background:</bold> Repeated exacerbations can accelerate the progression of COPD. Dupilumab is a human monoclonal antibody that blocks signaling of interleukin-4/13, key and central drivers in type 2 inflammation. In BOREAS and NOTUS, dupilumab reduced exacerbations and improved lung function in patients with COPD and type 2 inflammation. Safety was consistent with the known dupilumab safety profile. However, the impact of dupilumab on recurrent exacerbations is still unknown. <bold>Aims & objectives:</bold> To examine the association between dupilumab and recurrent moderate or severe exacerbations within 30 days of the first exacerbation in patients with COPD. <bold>Methods:</bold> Patients from BOREAS (<ext-link>NCT03930732</ext-link>) and NOTUS (<ext-link>NCT04456673</ext-link>) with COPD, moderate-to-severe airflow limitation, and type 2 inflammation (screening blood eosinophils ≥300 cells/µL) on triple therapy, received add-on dupilumab 300 mg q2w or placebo for 52 weeks. The frequency of repeat exacerbation within 30 days of the end of the index exacerbation was assessed in the pooled intention-to-treat population subgroup who experienced ≥2 exacerbations. <bold>Results:</bold> Of the patients receiving dupilumab who experienced ≥2 exacerbations (n=132), 16 (12.1%) had repeated moderate (15 [11.4%]) or severe (1 [0.8%]) exacerbations within 30 days of the end of the first exacerbation. Of the patients receiving placebo who had ≥2 exacerbations (n=190), 33 (17.4%) experienced repeated moderate (30 [15.8%]) or severe (3 [1.6%]) exacerbations within 30 days. <bold>Conclusion:</bold> Dupilumab reduced the number of recurrent moderate or severe exacerbations within 30 days in patients with COPD and type 2 inflammation with ≥2 exacerbations.