Effect of Tezepelumab on Exacerbations in Patients With Moderate to Very Severe Chronic Obstructive Pulmonary Disease Based on Inclusion or Exclusion of Antibiotic Use in the Definition of Moderate Exacerbations: Data From the Phase 2a COURSE Study

Abstract Rationale: Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin (TSLP), an epithelial cytokine that plays an upstream role in chronic obstructive pulmonary disease (COPD). In the phase 2a, multicenter, double-blind COURSE study (NCT04039113), tezepelumab reduced the annualized rate of COPD exacerbations that were moderate (resulting in systemic corticosteroids [SCS] and/or antibiotics use for ≥3 days [or one depot injection]) or severe (leading to hospitalization or death) by 37% versus placebo in patients with a baseline blood eosinophil count (BEC) of ≥150 cells/µL (95% CI: 7-57; rate ratio: 0.63 [95% CI: 0.43-0.93]). No reductions in exacerbations were observed in patients with BECs of <150 cells/µL (rate ratio: 1.19 [95% CI: 0.75-1.90]). It is not known whether the exacerbation reduction observed with tezepelumab varies based on whether moderate exacerbations with antibiotic use alone are counted. This exploratory analysis evaluated the efficacy of tezepelumab versus placebo in patients from COURSE, grouped by baseline BEC, in reducing COPD exacerbations based on whether antibiotic use alone was a criterion for moderate exacerbations. Methods: Patients (40-80 years old) 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 the annualized rate of moderate or severe COPD exacerbations over 52 weeks in patients overall and by baseline BEC subgroup (≥150 cells/μL and <150 cells/μL) based on whether antibiotic use (for ≥3 days) alone was included in the definition of a moderate exacerbation during the study. Results: Overall, 165 patients received tezepelumab and 168 received placebo. During the study, there were a small number of moderate exacerbations with antibiotic use and without SCS use. When moderate exacerbations treated with antibiotics alone were excluded, tezepelumab recipients overall and patients with a baseline BEC ≥150 cells/µL experienced 20% and 39% fewer COPD exacerbations versus placebo, respectively, over 52 weeks. For moderate exacerbations treated with antibiotics alone, tezepelumab recipients overall and those with a baseline BEC of ≥150 cells/µL had 10% and 21% fewer exacerbations versus placebo, respectively, over 52 weeks. No reductions were seen in patients with a BEC <150 cells/μL (Table). Conclusions: Compared with placebo recipients, tezepelumab recipients overall and those with baseline BECs of ≥150 cells/µL had reduced rates of COPD exacerbations, regardless of whether moderate exacerbations were treated with SCS or antibiotics alone.