Time to first moderate or severe COPD exacerbation with tezepelumab (COURSE)

<bold>Background:</bold> In COURSE (<ext-link>NCT04039113</ext-link>), tezepelumab numerically reduced the annualized rate of moderate or severe COPD exacerbations (overall by 17% [<italic>p</italic>=0.1042]; in patients with a blood eosinophil count [BEC] ≥150 cells/µL by 37%) and severe COPD exacerbations by 48% vs placebo over 52 weeks. <bold>Objective:</bold> Assess the efficacy of tezepelumab in delaying moderate or severe COPD exacerbations. <bold>Methods:</bold> COURSE was a phase 2a, randomized, double-blind, placebo-controlled study. Patients (≥40–80 years) with moderate to very severe COPD were randomized 1:1 to tezepelumab 420 mg or placebo subcutaneously every 4 weeks for up to 52 weeks. Eligible patients were receiving triple inhaled maintenance therapy and had ≥2 moderate or severe COPD exacerbations in the 12 months before enrolment. Time to first moderate or severe COPD exacerbation, and the proportions of patients with ≥1 of each, were assessed. <bold>Results:</bold> Of 333 randomized and treated patients (tezepelumab, n=165; placebo, n=168), 41%, 59% and 17% had baseline BECs <150, ≥150 and ≥300 cells/µL, respectively. Tezepelumab delayed time to first moderate or severe exacerbation vs placebo in the overall population (HR, 0.80 [95% CI: 0.61–1.06]; median days: 253 vs 214) and in those with baseline BECs <150 (HR, 0.88 [95% CI: 0.57–1.38]), ≥150 (HR, 0.74 [95% CI: 0.51–1.07]) and ≥300 cells/µL (HR, 0.51 [95% CI: 0.24–1.04]). Overall, time to first severe exacerbation was also delayed vs placebo (HR, 0.70 [95% CI: 0.36–1.33]). Fewer tezepelumab than placebo recipients had ≥1 moderate or severe exacerbation (57% vs 63%) or ≥1 severe exacerbation (10% vs 13%). <bold>Conclusion:</bold> Tezepelumab delayed the time to first moderate or severe COPD exacerbation, overall and across BEC subgroups.