Effect of Tezepelumab on Exacerbations in Patients with Severe, Uncontrolled Asthma, According to Baseline Body Mass Index: Results from the Phase 2b PATHWAY Study

Introduction and Objectives Tezepelumab is a human monoclonal antibody that blocks activity of thymic stromal lymphopoietin (TSLP), an epithelial cytokine implicated in asthma pathogenesis. In the PATHWAY study (NCT02054130), tezepelumab consistently reduced annualized asthma exacerbation rates (AAER) versus placebo in adults with severe uncontrolled asthma, irrespective of baseline disease characteristics. This analysis evaluated the efficacy of tezepelumab by baseline body mass index (BMI). Methods Patients aged 18–75 years with severe, uncontrolled asthma were randomized to receive subcutaneous tezepelumab (70 mg every 4 weeks [Q4W], 210 mg Q4W, 280 mg every 2 weeks) or placebo, for 52 weeks. AAER was estimated for baseline BMI subgroups of Results Overall, 550 patients were randomized. Lower BMI was associated with younger age, higher baseline blood eosinophil counts and higher fractional exhaled nitric oxide levels. Among placebo recipients, AAER over 52 weeks was similar by BMI subgroup (0.70–0.76 exacerbations per person-year). AAER over 52 weeks was reduced by 79% (95% CI: 57–89), 70% (95% CI: 41–85) and 50% (95% CI: 6–73) for pooled tezepelumab groups versus placebo in patients with a BMI of Conclusions Tezepelumab reduced exacerbations in patients with severe, uncontrolled asthma irrespective of baseline BMI, providing further evidence that tezepelumab can meaningfully reduce exacerbations in a broad population of patients with severe asthma.