Hector Ortega1, Andrew Menzies-Gow2, Jean-Pierre Llanos3, Mark Forshag3, Frank Albers4, Necdet Gunsoy5, Eric S Bradford4, Steven W Yancey4, Monica Kraft6. 1. Respiratory US Medical Affairs, GlaxoSmithKline, La Jolla, CA, USA. hectorortega15@hotmail.com. 2. Respiratory Medicine, Royal Brompton Hospital, London, UK. 3. Respiratory US Medical Affairs, GlaxoSmithKline, Research Triangle Park, NC, USA. 4. Respiratory Therapeutic Area Unit, GlaxoSmithKline, Research Triangle Park, NC, USA. 5. Clinical Statistics, GlaxoSmithKline, Stockley Park, Middlesex, UK. 6. Department of Medicine, University of Arizona, Tucson, AZ, USA.
Abstract
INTRODUCTION: Previous studies showed that mepolizumab significantly reduces exacerbations and oral corticosteroid use in patients with severe eosinophilic asthma. However, early studies reported inconsistent effects on lung function. This study specifically assessed the onset of clinical effect and the relationship of baseline blood eosinophil count of mepolizumab 100 mg subcutaneous (SC) administration on morning peak expiratory flow (AM PEF). METHODS: Post hoc analysis of data from two randomized, double-blind, placebo-controlled studies (MENSA, NCT01691521; MUSCA, NCT02281318) of 4-weekly mepolizumab 100 mg versus placebo in patients with severe eosinophilic asthma. Individual study results were generated using a mixed model repeated measures model controlling for multiple covariates and were combined using a fixed effects meta-analysis via inverse-variance weighting. RESULTS: Significant improvements in AM PEF after the first dose of mepolizumab 100 mg SC vs. placebo were seen as early as week 1 and continued to improve further with subsequent doses. The mean change in AM PEF was 26 L/min in the mepolizumab group compared to 4 L/min in the placebo group, p < 0.001. When the population was stratified by blood eosinophil thresholds the mean difference from placebo was 24 L/min (≥ 150 cells/µL), 27 L/min (≥ 300 cells/µL), and 34 L/min (≥ 500 cells/µL), p < 0.001 for all subgroups. The < 150 cells/µL (≥ 300 cells/µL in the previous year) group increased 13 L/min, while both 150 to < 300 cells/µL and 300 to < 500 cells/µL ranges demonstrated comparable changes (19 L/min and 17 L/min), respectively. CONCLUSION: Our analysis has shown early and consistent improvements in lung function measured by AM PEF using the study enrollment criterion of ≥ 150 eosinophils/µL. We also identified a relationship between baseline blood eosinophils and improvements in AM PEF with mepolizumab in patients with severe eosinophilic asthma. FUNDING: GlaxoSmithKline (study ID 208091).
RCT Entities:
INTRODUCTION: Previous studies showed that mepolizumab significantly reduces exacerbations and oral corticosteroid use in patients with severe eosinophilic asthma. However, early studies reported inconsistent effects on lung function. This study specifically assessed the onset of clinical effect and the relationship of baseline blood eosinophil count of mepolizumab 100 mg subcutaneous (SC) administration on morning peak expiratory flow (AM PEF). METHODS: Post hoc analysis of data from two randomized, double-blind, placebo-controlled studies (MENSA, NCT01691521; MUSCA, NCT02281318) of 4-weekly mepolizumab 100 mg versus placebo in patients with severe eosinophilic asthma. Individual study results were generated using a mixed model repeated measures model controlling for multiple covariates and were combined using a fixed effects meta-analysis via inverse-variance weighting. RESULTS: Significant improvements in AM PEF after the first dose of mepolizumab 100 mg SC vs. placebo were seen as early as week 1 and continued to improve further with subsequent doses. The mean change in AM PEF was 26 L/min in the mepolizumab group compared to 4 L/min in the placebo group, p < 0.001. When the population was stratified by blood eosinophil thresholds the mean difference from placebo was 24 L/min (≥ 150 cells/µL), 27 L/min (≥ 300 cells/µL), and 34 L/min (≥ 500 cells/µL), p < 0.001 for all subgroups. The < 150 cells/µL (≥ 300 cells/µL in the previous year) group increased 13 L/min, while both 150 to < 300 cells/µL and 300 to < 500 cells/µL ranges demonstrated comparable changes (19 L/min and 17 L/min), respectively. CONCLUSION: Our analysis has shown early and consistent improvements in lung function measured by AM PEF using the study enrollment criterion of ≥ 150 eosinophils/µL. We also identified a relationship between baseline blood eosinophils and improvements in AM PEF with mepolizumab in patients with severe eosinophilic asthma. FUNDING: GlaxoSmithKline (study ID 208091).
Entities:
Keywords:
AM PEF; Anti-IL-5; Blood eosinophils; Lung function; Monoclonal antibody; Respiratory; Severe asthma
Authors: Shaila Shabbir; Isabelle J Pouliquen; Jane H Bentley; Eric S Bradford; Morrys C Kaisermann; Muna Albayaty Journal: Clin Pharmacol Drug Dev Date: 2019-07-17
Authors: Mark C Liu; Elisabeth H Bel; Oliver Kornmann; Wendy C Moore; Norihiro Kaneko; Steven G Smith; Neil Martin; Robert G Price; Steven W Yancey; Marc Humbert Journal: ERJ Open Res Date: 2022-01-10
Authors: Wendy C Moore; Oliver Kornmann; Marc Humbert; Claude Poirier; Elisabeth H Bel; Norihiro Kaneko; Steven G Smith; Neil Martin; Martyn J Gilson; Robert G Price; Eric S Bradford; Mark C Liu Journal: Eur Respir J Date: 2022-01-06 Impact factor: 16.671