Efficacy of Tezepelumab in Patients With Moderate to Very Severe Chronic Obstructive Pulmonary Disease With and Without Chronic Bronchitis: Phase 2a COURSE Study

Abstract Rationale: Tezepelumab, a human monoclonal antibody, blocks thymic stromal lymphopoietin (TSLP). In patients with moderate to very severe COPD from the phase 2a COURSE study (NCT04039113), tezepelumab reduced the annualized rate of moderate or severe COPD exacerbations over 52 weeks versus placebo (overall population: 17% [95% CI: −11, 39]; patients with baseline blood eosinophil counts (BECs) of ≥150 cells/µl: 37% [95% CI: 7, 57]). This post hoc analysis evaluated the efficacy of tezepelumab in patients from COURSE with and without chronic bronchitis (CB) by baseline BEC. Methods: COURSE was a multicenter, randomized, double-blind, placebo-controlled study. Patients (40-80 years) with moderate to very severe COPD were randomized 1:1 to receive tezepelumab 420 mg or placebo subcutaneously every 4 weeks for up to 52 weeks. This analysis assessed annualized rate of moderate or severe COPD exacerbations over 52 weeks and changes from baseline to week 52 in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) and St George's Respiratory Questionnaire (SGRQ) total score in patients with and without CB, overall and by baseline BEC (≥/<150 cells/μL). CB was defined based on patient responses to cough and phlegm questions in SGRQ at baseline. Results: Tezepelumab recipients with (n=225) and without (n=101) CB had 26% (95% CI: −6, 49) and 0% (95% CI: −70, 41) fewer COPD exacerbations over 52 weeks, respectively, than placebo recipients. Among patients with baseline BEC ≥150 cells/µL, tezepelumab recipients with and without CB had 28% (95% CI: −13, 55) and 56% (95% CI: 6, 79) fewer exacerbations than placebo recipients. Least-squares (LS) mean changes from baseline to week 52 in pre-BD FEV1 with tezepelumab versus placebo were 0.089 L (95% CI: 0.026, 0.153) and 0.070 L (95% CI: −0.011, 0.151) among those with CB and baseline BEC ≥150 cells/µL and <150 cells/µL, respectively, and −0.003 L (95% CI: −0.119, 0.113) and 0.016 L (95% CI: −0.087, 0.120) among those without CB and baseline BEC ≥150 cells/µL and <150 cells/µL, respectively. Improvements in SGRQ total score were observed with tezepelumab versus placebo in patients with baseline BEC ≥150 cells/µL, with and without CB (LS mean difference: −3.45 and −4.55, respectively) (Table). Conclusions: In patients with moderate to very severe COPD, tezepelumab recipients with baseline BEC ≥150 cells/µL with or without CB experienced fewer COPD exacerbations and greater numerical improvements in health-related quality of life over 52 weeks versus placebo; those with CB had numerical improvements in lung function.