BASELINE PERCENT PREDICTED FEV1 DOES NOT PREDICT A RESPONSE TO MEPOLIZUMAB IN PATIENTS WITH SEVERE EOSINOPHILIC ASTHMA: META-ANALYSIS FROM TWO PHASE 3 TRIALS

Abstract

SESSION TITLE: Monday Electronic Posters 4 SESSION TYPE: Original Inv Poster Discussion PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM PURPOSE: The MENSA (NCT01691521) and MUSCA (NCT02281318) trials showed that mepolizumab consistently reduced annualized asthma exacerbation rates in patients with severe eosinophilic asthma. There are several risk factors for exacerbations, including decreased pulmonary function. The effect of the approved dose of mepolizumab, 100 mg subcutaneous (SC), on exacerbations according to a patient’s baseline % predicted FEV1 has not been examined. METHODS: This post-hoc subgroup analysis investigated the annual rate of clinically significant exacerbations (requiring administration of systemic glucocorticoids for ≥3 days or an emergency department visit/hospitalization) in patients receiving mepolizumab or placebo according to baseline % predicted FEV1 at screening in 3 categories (≤ 60, > 60 – ≤ 80 and > 80%). Exacerbation rates in the meta-analysis were measured at week 32 for MENSA and week 24 for MUSCA. Analyses were performed using negative binomial regression and treatment differences combined across studies using fixed-effects inverse-variance weighted meta-analysis. RESULTS: Of the 936 patients, 489 (52%), 354 (38%) and 93 (10%) were identified as having a ≤ 60, > 60 – ≤ 80 and > 80% predicted FEV1 at screening, respectively. Clinically relevant reductions in exacerbation rates were observed in the meta-analysis with 100 mg SC mepolizumab versus placebo, in patients from all categories of obstruction (rate ratio [mepolizumab/placebo]: ≤ 60% predicted FEV1 is 0.51[95% confidence interval [CI]: 0.39,0.66]; > 60 - ≤ 80% predicted FEV1 is 0.39[95% CI: 0.26,0.58]; > 80% predicted FEV1 is 0.37[95% CI: 0.19,0.73]). There was a numerical trend of an increase in the proportion of patients not having a clinically significant exacerbation with mepolizumab treatment, compared to placebo, with increasing baseline lung function (odds ratio [mepolizumab v placebo]: ≤ 60% predicted FEV1 is 2.67[95% CI: 1.79,3.98]; > 60 - ≤ 80% predicted FEV1 is 3.18[95% CI: 1.92,5.28]; > 80% predicted FEV1 is 4.90[95% CI: 1.54,15.62]). CONCLUSIONS: Mepolizumab produced clinically relevant reductions in the exacerbation rate versus placebo in patients with severe eosinophilic asthma irrespective of baseline % predicted FEV1. This suggests that baseline airway obstruction is not a factor that predicts a response to mepolizumab although patients with less severe lung function impairment may experience increasing relative benefit. This is aligned with DREAM that showed in a covariate modelling analysis, baseline % predicted FEV1 did not predict a response to intravenous mepolizumab. CLINICAL IMPLICATIONS: This abstract provides health care professionals with clinically relevant information on the efficacy of mepolizumab in severe eosinophilic asthma patients stratified by severity of airflow obstruction. DISCLOSURES: Employee relationship with GSK Please note: >$100000 Added 03/15/2019 by Frank Albers, source=Web Response, value=Salary Employee relationship with GSK Please note: >$100000 Added 03/18/2019 by Eric Bradford, source=Web Response, value=Salary Employee relationship with GSK Please note: >$100000 Added 03/18/2019 by Eric Bradford, source=Web Response, value=Ownership interest Employee relationship with GSK Please note: $5001 - $20000 Added 03/13/2019 by Stephen Mallett, source=Web Response, value=Shares Speaker/Speaker's Bureau relationship with Novartis Please note: $1001 - $5000 Added 03/19/2019 by Andrew Menzies-Gow, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Teva Please note: $1001 - $5000 Added 03/19/2019 by Andrew Menzies-Gow, source=Web Response, value=Honoraria Advisory Committee Member relationship with Astra Zeneca Please note: $5001 - $20000 Added 03/19/2019 by Andrew Menzies-Gow, source=Web Response, value=Honoraria Advisory Committee Member relationship with Glaxo SmithKline Please note: $1001 - $5000 Added 03/19/2019 by Andrew Menzies-Gow, source=Web Response, value=Honoraria Scientific Medical Advisor relationship with Boehringer Ingelheim Please note: $1001 - $5000 Added 03/19/2019 by Andrew Menzies-Gow, source=Web Response, value=Honoraria Consultant relationship with Vectura Please note: $5001 - $20000 Added 03/19/2019 by Andrew Menzies-Gow, source=Web Response, value=Honoraria Advisory Committee Member relationship with Sanofi Please note: $1001 - $5000 Added 03/19/2019 by Andrew Menzies-Gow, source=Web Response, value=Honoraria Employee relationship with GlaxoSmithKline Please note: >$100000 Added 03/07/2019 by Jared Silver, source=Web Response, value=Salary Employee relationship with GlaxoSmithKline (estimated stock ownership by time of Chest) Please note: $20001 - $100000 Added 03/07/2019 by Jared Silver, source=Web Response, value=stock Employee relationship with GSK Please note: >$100000 Added 03/07/2019 by Steven Smith, source=Web Response, value=Salary Employee relationship with GSK Please note: $5001 - $20000 Added 03/07/2019 by Steven Smith, source=Web Response, value=Stock Employee relationship with GlaxoSmithKline Please note: >$100000 Added 03/18/2019 by Steven Yancey, source=Web Response, value=Salary