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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.

Introduction and Objectives In the phase 2b PATHWAY study (NCT02054130), tezepelumab reduced annualized asthma exacerbation rates (AAER) by up to 71% versus placebo in adults with severe, uncontrolled asthma. We evaluated the effect of tezepelumab on exacerbations in patients from PATHWAY with low and high bronchodilator reversibility. Methods Adults with severe, uncontrolled asthma were randomized to receive tezepelumab (70 mg every 4 weeks [Q4W], 210 mg Q4W or 280 mg every 2 weeks) or placebo for 52 weeks. AAER and the rate of exacerbations resulting in hospitalization or emergency room (ER) visits were estimated for patients with low ( Results Of 550 randomized patients, 299 and 251 had low and high FEV1 reversibility, respectively. Tezepelumab 210 mg (phase 3 dose) reduced AAER over 52 weeks by 70% (95% confidence interval [CI]: 41, 85) and 72% (95% CI: 32, 88) versus placebo in patients with low and high FEV1 reversibility, respectively. For pooled tezepelumab doses, AAER was reduced by 69% (95% CI: 50, 81) and 60% (95% CI: 26, 78) in the low and high groups, respectively. Data were similar for 70 and 280 mg. Exacerbations resulting in hospitalizations or ER visits were reduced by 85% (95% CI: 21, 97) and 78% (95% CI: −32, 96) versus placebo in patients with low and high FEV1 reversibility, respectively, for tezepelumab 210 mg, and by 84% (95% CI: 51, 94) and 64% (95% CI: −18, 89) in the pooled tezepelumab group, respectively. Conclusions Tezepelumab treatment reduced AAER irrespective of baseline bronchodilator reversibility, further supporting its potential benefits in a broad population of patients with severe asthma.

Introduction and objectives Dupilumab, a fully human anti-interleukin (IL)−4Rα monoclonal antibody that inhibits IL-4 and IL-13, key drivers of Type 2 inflammation, is approved for treatment of adults with inadequately controlled, moderate-to-severe atopic dermatitis. In the double-blind, placebo-controlled LIBERTY ASTHMA QUEST phase 3 study (NCT02414854), patients with asthma aged ≥12 years, without a minimum baseline eosinophil requirement, uncontrolled with medium-to-high-dose inhaled corticosteroids plus up to two additional controllers, received add-on dupilumab 200 mg or 300 mg or matched placebo every 2 weeks (q2w) for 52 weeks. For the intent-to-treat population, both dupilumab regimens significantly reduced annualized severe exacerbation rates during the 52 week treatment period, improved pre-bronchodilator forced expiratory volume in 1 s (FEV1) at Week 12, improved asthma symptoms/quality of life measures, and were generally well tolerated. This post hoc analysis assessed the efficacy of dupilumab by the number of exacerbations experienced prior to the study. Methods Annualized severe exacerbation rates during the 52 week treatment period and change from baseline in pre-bronchodilator FEV1 (L) at Week 12 and Week 24 were analyzed by subgroups of patients with ≥1,≥2,≥3, or ≥4 exacerbations in the prior year. Results Both dupilumab q2w doses vs placebo reduced severe exacerbations over the 52 week treatment period (p Conclusions Dupilumab significantly reduced severe exacerbations and improved FEV1 regardless of exacerbation history, with greater improvements observed with higher numbers of prior exacerbations, in patients with uncontrolled, moderate-to-severe asthma, and was generally well tolerated. Please refer to page A267 for declarations of interest related to this abstract.