Health outcomes after stopping long-term mepolizumab in severe eosinophilic asthma: COMET
- Mark C Liu1⇑,
- Elisabeth H Bel2,
- Oliver Kornmann3,
- Wendy C Moore4,
- Norihiro Kaneko5,
- Steven G Smith6,
- Neil Martin7,14,8,
- Robert G Price9,
- Steven W Yancey10 and
- Marc Humbert11,12,13
- 1Divisions of Allergy and Clinical Immunology, Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, MD, USA
- 2Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- 3IKF Pneumologie Frankfurt, Clinical Research Centre Respiratory Diseases, Frankfurt, Germany
- 4Department of Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA
- 5Department of Pulmonary Medicine, Kameda Medical Center, Kamogawa, Japan
- 6Respiratory Therapeutic Area, GlaxoSmithKline, Research Triangle Park, NC, USA
- 7Global Medical Affairs, GSK, Brentford, Middlesex, UK
- 8Institute for Lung Health, University of Leicester, Leicester, UK
- 9Biostatistics, GSK, Stevenage, Hertfordshire, UK
- 10Respiratory Therapeutic Area, GSK, Research Triangle Park, NC, USA
- 11Assistance Publique -Hôpitaux de Paris, Service de Pneumologie et Soins Intensifs Respiratoires, Hôpital Bicêtre, Le Kremlin-Bicêtre, Paris, France
- 12Université Paris-Saclay, Paris, France
- 13INSERM U999, Le Kremlin-Bicêtre, Paris, France
- 14Affiliation at the time of the study
- Mark Liu (mcl{at}jhmi.edu)
Abstract
Abstract
Asthma worsening and symptom control are clinically important health outcomes in patients with severe eosinophilic asthma. This analysis of COMET evaluated whether stopping versus continuing long-term mepolizumab therapy impacted these outcomes.
Patients with severe eosinophilic asthma with ≥3 years continuous mepolizumab treatment (via COLUMBA [NCT01691859] or COSMEX [NCT02135692] open label studies) were eligible to enter COMET (NCT02555371), a randomised, double-blind, placebo-controlled study. Patients were randomised 1:1 to continue mepolizumab 100 mg subcutaneous every four weeks or stop mepolizumab, plus standard of care asthma treatment. Patients could switch to open label mepolizumab following an exacerbation. Health outcome endpoints included time to first asthma worsening (composite endpoint: rescue use, symptoms, awakening at night and morning PEF), patient and clinician assessed global rating of asthma severity and overall perception of response to therapy, and unscheduled healthcare resource utilisation.
Patients who stopped mepolizumab showed increased risk of and shorter time to first asthma worsening compared with those who continued mepolizumab (Hazard Ratio [HR]:1.71 [95% CI: 1.17 2.52] p=0.006), including reduced asthma control (increased risk of first worsening in rescue use [HR:1.36 (95% CI 1.00 1.84) p=0.047] and morning PEF [HR:1.77 (95% CI 1.21 2.59) p=0.003]). There was a higher probability of any unscheduled healthcare resource use (HR:1.81 [95% CI: 1.31 2.49]; p<0.001) and patients and clinicians reported greater asthma severity and less favourable perceived response to therapy for patients who stopped versus continued mepolizumab.
These data suggest that patients with severe eosinophilic asthma continuing long-term mepolizumab treatment sustain clinically important improvements in health outcomes.
Footnotes
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Conflict of interests: MCL has received grants for clinical trials from Boehringer Ingelheim, GSK and Gossamer Bio and personal fees for participation in advisory boards from AstraZeneca, GSK and Gossamer Bio.
Conflict of interests: EHB reports grants from GSK and Teva; and personal fees from AstraZeneca, GSK, Novartis, Sanofi Regeneron, Sterna Biologicals, and Chiesi.
Conflict of interests: OK has received personal fees from AstraZeneca, GSK, Novartis, Boehringer Ingelheim, Sanofi Aventis and Roche.
Conflict of interests: WCM has received funding for clinical research and personal fees for participation in advisory boards from GSK, AstraZeneca and Sanofi Regeneron.
Conflict of interests: NK reports that he has nothing to declare.
Conflict of interests: SGS are employees of GSK and own stocks/shares.
Conflict of interests: NM is a former employee of GSK and owns stocks/shares.
Conflict of interests: RGP are employees of GSK and own stocks/shares.
Conflict of interests: SWY are employees of GSK and own stocks/shares.
Conflict of interests: MH received personal fees for consultancy services and speaking at conferences, and participation in clinical research projects with AstraZeneca, GSK, Novartis, Roche, Sanofi Regeneron and Teva; he has a research grant from GSK.
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- Received June 24, 2021.
- Accepted September 26, 2021.
- Copyright ©The authors 2021
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