Information de reference pour ce titreAccession Number: | 00006114-201709120-00006.
|
Author: | Havrdova, Eva MD, PhD; Arnold, Douglas L. MD; Cohen, Jeffrey A. MD; Hartung, Hans-Peter MD, PhD; Fox, Edward J. MD, PhD; Giovannoni, Gavin MD, PhD; Schippling, Sven MD; Selmaj, Krzysztof W. MD, PhD; Traboulsee, Anthony MD; Compston, D. Alastair S. PhD, FRS; Margolin, David H. MD, PhD; Thangavelu, Karthinathan PhD; Rodriguez, Claudio E. MD; Jody, Darlene MD; Hogan, Richard J. PhD; Xenopoulos, Panos PhD; Panzara, Michael A. MD, MPH; Coles, Alasdair J. MD, PhD; On behalf of CARE-MS I and CAMMS03409 Investigators
|
Institution: | From the Department of Neurology and Center for Clinical Neuroscience (E.H.), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; NeuroRx Research (D.L.A.), Montreal; Department of Neurology and Neurosurgery (D.L.A.), Montreal Neurological Institute, McGill University, Quebec, Canada; Mellen Center (J.A.C.), Cleveland Clinic, OH; Department of Neurology and Center for Neuropsychiatry (H.-P.H.), Medical Faculty, Heinrich-Heine University, Dusseldorf, Germany; MS Clinic of Central Texas (E.J.F.), Central Texas Neurology Consultants, Round Rock; Queen Mary University of London (G.G.), Barts and The London School of Medicine, UK; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich and University of Zurich, Switzerland; Department of Neurology (K.W.S.), Medical University of Lodz, Poland; The University of British Columbia (A.T.), Vancouver, Canada; Department of Clinical Neurosciences (D.A.S.C., A.J.C.), University of Cambridge, UK; Sanofi (D.H.M., K.T., C.E.R., D.J., M.A.P.), Cambridge, MA; Evidence Scientific Solutions (R.J.H.), Sydney, NSW, Australia; and Evidence Scientific Solutions (P.X.), Philadelphia, PA. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.
|
Title: | |
Source: | Neurology. 89(11):1107-1116, September 12, 2017.
|
Abstract: | Objective: To evaluate 5-year efficacy and safety of alemtuzumab in treatment-naive patients with active relapsing-remitting MS (RRMS) (CARE-MS I; NCT00530348).
Methods: Alemtuzumab-treated patients received treatment courses at baseline and 12 months later; after the core study, they could enter an extension (NCT00930553) with as-needed alemtuzumab retreatment for relapse or MRI activity. Assessments included annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW; >=1-point Expanded Disability Status Scale [EDSS] score increase [>=1.5 if baseline EDSS = 0]), 6-month confirmed disability improvement (CDI; >=1-point EDSS decrease [baseline score >=2.0]), no evidence of disease activity (NEDA), brain volume loss (BVL), and adverse events (AEs).
Results: Most alemtuzumab-treated patients (95.1%) completing CARE-MS I enrolled in the extension; 68.5% received no additional alemtuzumab treatment. ARR remained low in years 3, 4, and 5 (0.19, 0.14, and 0.15). Over years 0-5, 79.7% were free of 6-month CDW; 33.4% achieved 6-month CDI. Most patients (61.7%, 60.2%, and 62.4%) had NEDA in years 3, 4, and 5. Median yearly BVL improved over years 2-4, remaining low in year 5 (years 1-5: -0.59%, -0.25%, -0.19%, -0.15%, and -0.20%). Exposure-adjusted incidence rates of most AEs declined in the extension relative to the core study. Thyroid disorder incidences peaked at year 3 and subsequently declined.
Conclusions: Based on these data, alemtuzumab provides durable efficacy through 5 years in the absence of continuous treatment, with most patients not receiving additional courses.
ClinicalTrials.gov identifier: NCT00530348; NCT00930553.
Classification of evidence: This study provides Class III evidence that alemtuzumab durably improves efficacy outcomes and slows BVL in patients with RRMS.
(C) 2017 American Academy of Neurology
|
References: | 1. Weber MS, Hemmer B. Cooperation of B cells and T cells in the pathogenesis of multiple sclerosis. Results Probl Cell Differ 2010;51:115-126.
2. Hu Y, Turner MJ, Shields J, et al. Investigation of the mechanism of action of alemtuzumab in a human CD52 transgenic mouse model. Immunology 2009;128:260-270.
3. Rao SP, Sancho J, Campos-Rivera J, et al. Human peripheral blood mononuclear cells exhibit heterogeneous CD52 expression levels and show differential sensitivity to alemtuzumab mediated cytolysis. PLoS One 2012;7:e39416.
4. Cox AL, Thompson SA, Jones JL, et al. Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis. Eur J Immunol 2005;35:3332-3342.
5. CAMMS223 Trial Investigators, Coles AJ, Compston DA, et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med 2008;359:1786-1801.
6. Cohen JA, Coles AJ, Arnold DL, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet 2012;380:1819-1828.
7. Coles AJ, Twyman CL, Arnold DL, et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet 2012;380:1829-1839.
8. LEMTRADA [Summary of Product Characteristics] [online]. Oxford, United Kingdom: Genzyme Therapeutics, Ltd. Available at: ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003718/WC500150521.pdf. Accessed May 30, 2014.
9. LEMTRADA (Alemtuzumab), for Intravenous Injection [Prescribing Information]. Cambridge, MA: Genzyme Corporation; 2014.
10. Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology 2014;83:278-286.
11. Liu GF, Wang J, Liu K, Snavely DB. Confidence intervals for an exposure adjusted incidence rate difference with applications to clinical trials. Stat Med 2006;25:1275-1286.
12. Comi G. Shifting the paradigm toward earlier treatment of multiple sclerosis with interferon beta. Clin Ther 2009;31:1142-1157.
13. Rush CA, MacLean HJ, Freedman MS. Aggressive multiple sclerosis: proposed definition and treatment algorithm. Nat Rev Neurol 2015;11:379-389.
14. Zivadinov R, Reder AT, Filippi M, et al. Mechanisms of action of disease-modifying agents and brain volume changes in multiple sclerosis. Neurology 2008;71:136-144.
15. Multiple Sclerosis Therapy Consensus Group (MSTCG), Wiendl H, Toyka KV, et al. Basic and escalating immunomodulatory treatments in multiple sclerosis: current therapeutic recommendations. J Neurol 2008;255:1449-1463.
16. Scalfari A, Neuhaus A, Degenhardt A, et al. The natural history of multiple sclerosis: a geographically based study 10: relapses and long-term disability. Brain 2010;133:1914-1929.
17. Fisniku LK, Brex PA, Altmann DR, et al. Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. Brain 2008;131:808-817.
18. Popescu V, Agosta F, Hulst HE, et al. Brain atrophy and lesion load predict long term disability in multiple sclerosis. J Neurol Neurosurg Psychiatry 2013;84:1082-1091.
19. Rieckmann P. Concepts of induction and escalation therapy in multiple sclerosis. J Neurol Sci 2009;277(suppl 1):S42-S45.
20. Coles AJ, Fox E, Vladic A, et al. Alemtuzumab versus interferon beta-1a in early relapsing-remitting multiple sclerosis: post-hoc and subset analyses of clinical efficacy outcomes. Lancet Neurol 2011;10:338-348.
21. Fox EJ, Arnold DL, Cohen JA, et al. Durable efficacy of alemtuzumab on clinical outcomes over 5 years in CARE-MS II with most patients free from treatment for 4 years. Mult Scler 2015;21(suppl 11):P1102.
22. Fisher E, Rudick RA, Cutter G, et al. Relationship between brain atrophy and disability: an 8-year follow-up study of multiple sclerosis patients. Mult Scler 2000;6:373-377.
23. Jacobsen C, Hagemeier J, Myhr KM, et al. Brain atrophy and disability progression in multiple sclerosis patients: a 10-year follow-up study. J Neurol Neurosurg Psychiatry 2014;85:1109-1115.
24. Sormani MP, Arnold DL, De Stefano N. Treatment effect on brain atrophy correlates with treatment effect on disability in multiple sclerosis. Ann Neurol 2014;75:43-49.
25. Barkhof F, Cohen JA, Coles A, et al. RRMS patients switching from SC IFNB-1a to alemtuzumab in the CARE-MS I and II extension study have a reduced rate of brain volume loss (P6.183). Neurology 2016;86(suppl):16.
26. Schneider DF, Chen H. New developments in the diagnosis and treatment of thyroid cancer. CA Cancer J Clin 2013;63:374-394.
27. Butzkueven H, Kappos L, Pellegrini F, et al. Efficacy and safety of natalizumab in multiple sclerosis: interim observational programme results. J Neurol Neurosurg Psychiatry 2014;85:1190-1197.
28. O'Connor P, Goodman A, Kappos L, et al. Long-term safety and effectiveness of natalizumab redosing and treatment in the STRATA MS Study. Neurology 2014;83:78-86.
29. Bloomgren G, Richman S, Hotermans C, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med 2012;366:1870-1880.
|
Language: | English.
|
Document Type: | Article.
|
Journal Subset: | Clinical Medicine. Life & Biomedical Sciences.
|
ISSN: | 0028-3878
|
NLM Journal Code: | 0401060, nz0
|
DOI Number: | https://dx.doi.org/10.1212/WNL.0...- ouverture dans une nouvelle fenêtre
|
Annotation(s) | |
|
|