Assessment of the long-term safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma - 04/05/19
Abstract |
Background |
Mepolizumab has demonstrated favorable safety and efficacy profiles in placebo-controlled trials of 12 months' duration or less; however, long-term data are lacking.
Objective |
We sought to evaluate the long-term safety and efficacy of mepolizumab in patients with severe eosinophilic asthma (SEA).
Methods |
COLUMBA (Open-label Long Term Extension Safety Study of Mepolizumab in Asthmatic Subjects, NCT01691859) was an open-label extension study in patients with SEA previously enrolled in DREAM (Dose Ranging Efficacy And Safety With Mepolizumab in Severe Asthma, NCT01000506). Patients received 100 mg of subcutaneous mepolizumab every 4 weeks plus standard of care until a protocol-defined stopping criterion was met. Safety end points included frequency of adverse events (AEs), serious AEs, and AEs of special interest. Efficacy end points included annualized exacerbation rates, changes from baseline in Asthma Control Questionnaire 5 scores, and blood eosinophil counts. Immunogenicity was also assessed.
Results |
Overall, 347 patients were enrolled for an average of 3.5 years (maximum, 4.5 years; total exposure, 1201 patient-years). On-treatment AEs were reported in 94% of patients (exposure-adjusted rate, 3688 events/1000 patient-years). The most frequently reported on-treatment AEs were respiratory tract infection, headache, bronchitis, and asthma worsening. Seventy-nine (23%) patients experienced 1 or more on-treatment serious AEs; there were 6 deaths, none of which were assessed as related to mepolizumab. For patients with 156 weeks or greater enrollment, the exacerbation rate was 0.74 events/y (weeks 0–156), a 56% reduction from the off-treatment period between DREAM and COLUMBA. For all patients, at the first postbaseline assessment, the mean Asthma Control Questionnaire 5 score was reduced by 0.47 points, and blood eosinophil counts were reduced by 78%, with similar improvements maintained throughout the study. The immunogenicity profile (8% anti-drug antibodies) was consistent with previous studies.
Conclusion |
These data support the long-term safety and efficacy of mepolizumab in patients with SEA.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Mepolizumab, severe eosinophilic asthma, long-term safety, extension study
Abbreviations used : ACQ-5, ADA, AE, AESI, COLUMBA, COSMOS, DREAM, EXCELS, MENSA, MUSCA, NAb, SAE, SEA, SIRIUS
Plan
| This study was funded by GlaxoSmithKline (GSK ID: MEA115666; ClinicalTrials.gov number: NCT01691859). |
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| Disclosure of potential conflict of interest: S. Khatri reports being an investigator in clinical trials in relation to GlaxoSmithKline and Boston Scientific, for which her institution is compensated for time related to the study. W. Moore reports receiving research grants from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Novartis, Pearl Therapeutics, Sanofi Regeneron, and the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI), and has been an advisory board consultant for AstraZeneca and Sanofi Regeneron. P. G. Gibson reports receiving personal fees from AstraZeneca, GlaxoSmithKline, and Novartis and a research grant from GlaxoSmithKline and the National Health and Medical Research Council (NHMRC). R. Leigh reports receiving honoraria and speakers' fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, and TEVA; his institution has also received research funding from AstraZeneca, GlaxoSmithKline, MedImmune, Novartis, and Sanofi for clinical trials in which he was a site investigator. A. Bourdin reports receiving personal fees, research grants, and nonfinancial support from GlaxoSmithKline; personal fees and nonfinancial support from AstraZeneca and Novartis; research grants from MSD; research grants and personal fees from Actelion; and personal fees and nonfinancial support from Chiesi. J. Maspero reports attending focus groups and boards for AstraZeneca and receiving personal fees from Novartis, AstraZeneca, GlaxoSmithKline, Sanofi, and Uriach. M. Barros reports receiving honoraria from Boehringer Ingelheim and Grifols for lectures and Advisory boards and has been involved as Principal Investigator in clinical trials for GlaxoSmithKline, Pearl Therapeutics, Sanofi Aventis, and Chiesi. R. Buhl reports personal fees from AstraZeneca, Chiesi, Teva, and Cipla; grants and personal fees from Boehringer Ingelheim, Novartis, and Roche; and grants from GlaxoSmithKline, all of which are outside the submitted work. P. Howarth, F. C. Albers, E. S. Bradford, M. Gilson, R. G. Price, and S. W. Yancy are all employees of GlaxoSmithKline and hold stocks/shares in GlaxoSmithKline. H. Ortega is a former employee of GlaxoSmithKline and holds stocks/shares in GlaxoSmithKline. |
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| Anonymized individual participant data and study documents can be requested for further research from www.clinicalstudydatarequest.com |
Vol 143 - N° 5
P. 1742 - mai 2019 Retour au numéro
Article précédent
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