THE EFFECT OF TEZEPELUMAB ON EXACERBATIONS IN PATIENTS WITH SEVERE, UNCONTROLLED ASTHMA ACCORDING TO BASELINE INHALED CORTICOSTEROID DOSE: RESULTS FROM THE PHASE 2B PATHWAY STUDY

Abstract

SESSION TITLE: Updates in the Management of Severe Asthma SESSION TYPE: Original Investigations PRESENTED ON: October 18-21, 2020 PURPOSE: Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, an epithelial cytokine implicated in asthma pathogenesis. In the phase 2b PATHWAY study (NCT02054130), tezepelumab significantly reduced annualized asthma exacerbation rates (AAER) by up to 71% versus placebo in adults with severe, uncontrolled asthma. This post hoc analysis evaluated the effect of tezepelumab on AAER and forced expiratory volume in 1 second (FEV1) in patients from PATHWAY taking medium-dose (MD) or high-dose (HD) inhaled corticosteroids (ICS) at baseline. METHODS: Adults (18–75 years) with severe, uncontrolled asthma were randomized to receive subcutaneous tezepelumab (70mg every 4 weeks [Q4W], 210mg Q4W, 280mg every 2 weeks) or placebo for 52 weeks. AAER and FEV1 were determined in patients taking MD (250–500μg/day of fluticasone propionate [FP] or equivalent) or HD (>500μg/day FP or equivalent) ICS at baseline. Data are reported for tezepelumab 210mg and pooled tezepelumab doses. RESULTS: Overall, 550 patients were randomized to placebo (n=138) or tezepelumab 70mg (n=138), 210mg (n=137) or 280mg (n=137). Patients taking HD ICS (n=269) had more exacerbations in the prior year (mean: 2.6 vs 2.2), higher fractional exhaled nitric oxide levels (median: 24.3 vs 20.5 ppb) and lower post-bronchodilator FEV1 reversibility (median: 287.0 vs 340.0 mL) at baseline than those taking MD ICS (n=281), and higher occurrence of nasal polyps (18.6% vs 11.4%) and maintenance oral corticosteroid (OCS) use (18.6% vs 0.4%). Over 52 weeks, AAER in placebo-treated patients was higher in the HD ICS group than in the MD ICS group (1.12 [95% confidence interval (CI): 0.76–1.66] vs 0.38 [95% CI: 0.24–0.61], respectively). For tezepelumab 210mg, AAER was reduced by 77% (95% CI: 54–89) and 60% (95% CI: 8–83) versus placebo in the HD and MD ICS groups, respectively. Results were similar for pooled tezepelumab doses versus placebo (HD ICS, 74% [95% CI: 57–84]; MD ICS, 52% [95% CI: 12–73]). Compared with placebo, the least squares mean change from baseline in FEV1 at week 52 was 160mL (95% CI: 10–300) and 140mL (95% CI: 0–280) in patients taking HD and MD ICS, respectively, in the tezepelumab 210mg group, and 190mL (95% CI: 70–310) and 120mL (95% CI: 10–230), respectively, in the pooled tezepelumab dose group. CONCLUSIONS: Patients with severe, uncontrolled asthma taking HD ICS had more exacerbations in the prior year and higher baseline maintenance OCS use than those taking MD ICS, which is consistent with patients taking HD ICS having more severe disease. Treatment with tezepelumab reduced exacerbations and improved FEV1 versus placebo in both ICS dose groups, with a trend of greater effects in patients taking HD ICS. CLINICAL IMPLICATIONS: This study further supports the potential benefits of tezepelumab treatment in patients with severe, uncontrolled asthma, irrespective of pre-treatment maintenance ICS dose. 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