Abstract Rationale Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin (TSLP), an epithelial cytokine implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). In the COURSE phase 2a study (NCT04039113), tezepelumab numerically reduced the annualized rate of moderate or severe COPD exacerbations over 52 weeks versus placebo in the overall population of patients with moderate to very severe COPD, with greater efficacy in patients with a baseline blood eosinophil count (BEC) of ≥ 150 cells/µL. No exacerbation reduction was observed among patients with a baseline BEC of 150 cells/µL. This post hoc analysis of COURSE evaluated the effect of tezepelumab on exacerbation-related systemic corticosteroid (SCS) use in patients with a baseline BEC of ≥ 150 cells/µL and 150 cells/µL. Methods COURSE was a phase 2a, multicenter, randomized, placebo-controlled study. Patients (40-80 years old) 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. A single depot injection dose of corticosteroid was considered equivalent to a 3-day course of SCS. The number of days of SCS use with the reason for treatment recorded as ‘COPD exacerbation per protocol’ was assessed over 52 weeks in patients with a baseline BEC of ≥ 150 cells/µL and 150 cells/µL. Results Overall, 333 patients received tezepelumab (n = 165) or placebo (n = 168), of whom 196 patients had a baseline BEC of ≥ 150 cells/µL and 137 patients had a baseline BEC of 150 cells/µL. The proportion of patients who received SCS for a COPD exacerbation was numerically lower with tezepelumab versus placebo among those with baseline BEC ≥ 150 cells/µL or 150 cells/µL, with a greater difference in those with BEC ≥ 150 cells/µL (Table). Among patients with baseline BEC ≥ 150 cells/µL, tezepelumab recipients had a numerically lower mean and total number of days of SCS treatment associated with COPD exacerbations compared with placebo recipients (Table). Conclusions In patients with moderate to very severe COPD and a baseline BEC of ≥ 150 cells/µL, tezepelumab treatment was associated with reduced COPD exacerbation-related SCS use compared with placebo. This post hoc analysis further supports the efficacy of tezepelumab in patients with moderate to very severe COPD with a baseline BEC of ≥ 150 cells/µL. This abstract is funded by: AstraZeneca & Amgen
Criner et al. (Fri,) studied this question.