PT - JOURNAL ARTICLE AU - Wendy C. Moore AU - Oliver Kornmann AU - Marc Humbert AU - Claude Poirier AU - Elisabeth H. Bel AU - Norihiro Kaneko AU - Steven G. Smith AU - Neil Martin AU - Martyn J. Gilson AU - Robert G. Price AU - Eric S. Bradford AU - Mark C. Liu TI - Stopping <em>versus</em> continuing long-term mepolizumab treatment in severe eosinophilic asthma (COMET study) AID - 10.1183/13993003.00396-2021 DP - 2021 Jan 01 TA - European Respiratory Journal PG - 2100396 4099 - http://erj.ersjournals.com/content/early/2021/07/08/13993003.00396-2021.short 4100 - http://erj.ersjournals.com/content/early/2021/07/08/13993003.00396-2021.full AB - The long-term efficacy and safety of mepolizumab for treatment of severe eosinophilic asthma are well established. Here, we examine the clinical impact of stopping mepolizumab after long-term use.COMET (NCT02555371) was a randomised, double-blind, placebo-controlled, parallel-group, multicenter study. Patients who had completed COLUMBA (NCT01691859) or COSMEX (NCT02135692) and received continuous mepolizumab treatment for ≥3 years were randomised 1:1 to stop (switch to placebo) or continue subcutaneous mepolizumab 100 mg every 4 weeks for 52 weeks. Primary endpoint: time to first clinically significant exacerbation; secondary endpoints: time to first exacerbation requiring hospitalisation/emergency department visit, time to decrease in asthma control (≥0.5-point increase in Asthma Control Questionnaire-5 score from COMET baseline), and blood eosinophil count ratio to COMET baseline. Safety was assessed.Patients stopping (n=151) versus continuing (n=144) mepolizumab had significantly shorter times to first clinically significant exacerbation (hazard ratio: 1.61 [95% confidence interval: 1.17,2.22]; p=0.004) and decrease in asthma control (hazard ratio: 1.52 [1.13,2.02]; p=0.005), and higher blood eosinophil counts at Week 52 (270 versus 40 cells·µL−1; ratio [stopping versus continuing]: 6.19 [4.89, 7.83]; p&lt;0.001). Differences in efficacy outcomes between groups were observed when assessed from Week 12 (16 weeks after last mepolizumab dose). Exacerbations requiring hospitalisation/emergency department visit were rare. Adverse events in patients continuing mepolizumab were consistent with previous studies. For patients who stopped mepolizumab, the safety profile was consistent with other eosinophilic asthma populations.Patients who stopped mepolizumab had an increase in exacerbations and reduced asthma control versus those who continued.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Moore reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; grants and personal fees from GlaxoSmithKline, grants and personal fees from AstraZeneca, grants and personal fees from Sanofi Regeneron, outside the submitted work.Conflict of interest: Dr. Kornmann reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; personal fees from AstraZeneca, personal fees from GlaxoSmithKline, personal fees from Novartis, personal fees from Boehringer Ingelheim, personal fees from Sanofi Aventis, personal fees from Roche, outside the submitted work.Conflict of interest: Dr. Humbert reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; personal fees from AstraZeneca, grants and personal fees from GlaxoSmithKline, personal fees from Novartis, personal fees from Roche, personal fees from Sanofi, personal fees from TEVA, outside the submitted work.Conflict of interest: Dr. Poirier reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; personal fees from GlaxoSmithKline, personal fees from Novartis, personal fees from Sanofi, personal fees from Boehringer Ingelheim, outside the submitted work.Conflict of interest: Dr. Bel reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; grants and personal fees from AstraZeneca, grants and personal fees from GlaxoSmithKline, grants and personal fees from Novartis, grants and personal fees from Teva, personal fees from Sanofi/Regeneron, personal fees from Sterna Biologicals, personal fees from Chiesi, outside the submitted work.Conflict of interest: Dr. Kaneko reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study.Conflict of interest: Dr. Smith reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; personal fees and other from GlaxoSmithKline, outside the submitted work.Conflict of interest: Dr. Martin reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; personal fees and other from GlaxoSmithKline, outside the submitted work.Conflict of interest: Dr. Gilson reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; personal fees and other from GlaxoSmithKline, outside the submitted work.Conflict of interest: Mr. Price reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; personal fees and other from GlaxoSmithKline, outside the submitted work.Conflict of interest: Dr. Bradford reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; personal fees and other from GlaxoSmithKline, outside the submitted work.Conflict of interest: Dr. Liu reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; grants from Boehringer Ingelheim, grants from GlaxoSmithKline, grants from MedImmune, grants from Mereo BioPharm, grants from GossamerBio, outside the submitted work.