Alemtuzumab: A Review of Its Use in Patients with Relapsing Multiple Sclerosis
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Alemtuzumab (Lemtrada™) is a humanized therapeutic monoclonal antibody, which has been approved for use in patients with B-cell chronic lymphocytic leukaemia for several years, and has recently become approved in the EU and several other countries for use in adult patients with active relapsing-remitting multiple sclerosis. This article reviews the available pharmacological properties of intravenous infusions of alemtuzumab and its clinical efficacy and tolerability in adult patients with relapsing-remitting multiple sclerosis. Alemtuzumab is an effective treatment for patients with relapsing-remitting multiple sclerosis, and has a generally acceptable tolerability profile. In phase III trials, it was shown to be more effective than a current first-line treatment, subcutaneous interferon beta-1a, in decreasing relapse rate in treatment-naïve and previously treated patients and in decreasing disability progression in previously treated patients. Of note, these results appear to have extended into the long-term follow-up, despite no further treatment. There was an increased risk of autoimmunity and infection associated with alemtuzumab in these trials; while these adverse events were generally mild to moderate, some were severe. Alemtuzumab is a highly convenient treatment, requiring hospital attendance for an intravenous infusion for a handful of days on two consecutive years, with no treatment required in between; however, this convenience is counterbalanced by the need for regular monitoring for the increased risk of autoimmunity. More investigation is required before final conclusions can be drawn on the correct placement of alemtuzumab in multiple sclerosis treatment; however, it is of a certainty a welcome addition to the treatment options for these patients.
The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.
- 1.World Health Organisation and Multiple Sclerosis International Federation. Atlas: multiple sclerosis resources in the world 2008. 2008. http://www.who.int/mental_health/neurology/Atlas_MS_WEB.pdf?ua=1. Accessed 29 Jan 2014.
- 3.National Institute for Health and Care Excellence. Multiple sclerosis: management of multiple sclerosis in primary and secondary care. NICE guideline. 2003. http://www.nice.org.uk/nicemedia/live/10930/29199/29199.pdf. Accessed 4 Nov 2013.
- 4.Goodin DS, Frohman EM, Garmany GP Jr, et al. Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology. 2002;58(2):169–78.PubMedCrossRefGoogle Scholar
- 7.Genzyme Therapeutics Ltd. Lemtrada™ (alemtuzumab 12 mg concentrate for solution for infusion): EU summary of product characteristics. 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003718/WC500150521.pdf. Accessed 16 Oct 2013.
- 10.Helliwell CL, Thompson SAJ, Jones J, et al. Alemtuzumab (campath-1H) treatment for multiple sclerosis reduces pro-inflammatory cytokine secretion from peripheral blood mononuclear cells [abstract]. J Neurol Neurosurg Psychiatry. 2009;80(11).Google Scholar
- 16.Hartung HP, Arnold DL, Cohen J, et al. Lymphocyte subset dynamics following alemtuzumab treatment in the CARE-MS I study [abstract no. P935]. In: 28th annual congress of the European Committee for Treatment and Research in Multiple Sclerosis; 10–13 Oct 2012; Lyon.Google Scholar
- 17.Kasper L, Arnold D, Cohen J. Lymphocyte subset dynamics following alemtuzumab treatment in the CARE-MS II study [abstract no. P531]. In: 29th annual congress of the European Committee for Research and Treatment in Multiple Sclerosis; 2–5 Oct 2013; Copenhagen.Google Scholar
- 24.Fox EAD, Cohen J, Coles AJ. Durable efficacy of alemtuzumab in relapsing-remitting multiple sclerosis patients who participated in the CARE-MS studies: 3 year follow-up [abstract no. S41.001]. Neurology. 2013;80 (1_MeetingAbstracts).Google Scholar
- 25.Jung Henson L, Arnold DL, Cohen JA, et al. Durable effects of alemtuzumab on relapse rates over time in CARE-MS II. [abstract no. 1357]. 27th annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and the 5th cooperative meeting of CMSC-ACTRIMS 29 May–1 Jun 2013; Orlando, FL.Google Scholar
- 26.Crayton H, Arnold DL, Cohen JA, et al. Alemtuzumab’s effects on disability outcomes occur early in CARE-MS II. [abstract no. 1639]. In: 27th annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and the 5th cooperative meeting of CMSC-ACTRIMS; 29 May–1 Jun 2013; Orlando, FL.Google Scholar
- 27.Krieger S, Arnold DL, Cohen JA, et al. Alemtuzumab is efficacious in highly active RRMS patients in CARE-MS II. [abstract no. DX01]. In: 27th annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and the 5th cooperative meeting of CMSC-ACTRIMS; 29 May–1 Jun 2013; Orlando, FL.Google Scholar
- 28.Gupta A, Arnold DL, Cohen JA, et al. Alemtuzumab improves quality of life compared to SC IFNB-1A in CARE-MS I [abstract no. DX40 plus poster]. In: Annual Meeting of the Consortium of Multiple Sclerosos Centers (CMSC); 30 May–2 June 2012; San Diego, CA.Google Scholar
- 29.Selmaj K, Arnold DL, Cohen J, et al. Alemtuzumab improves patient-reported quality of life in relapsing-remitting multiple sclerosis: CARE-MS I and II phase 3 trials [abstract no. P338 plus poster presented at the 22nd Meeting of the European Neurological Society, Prague, 9–12 Jun 2012]. J Neurol. 2012;259(Suppl. 1):S65–6.Google Scholar
- 30.Arroyo R, Arnold DL, Cohen JA, et al. Alemtuzumab improves quality of life compared to SC IFNB-1a in CARE-MS II [abstract no. P531]. J Neurol. 2013;260(Suppl. 1):S121.Google Scholar
- 31.Havrdova E, Arnold DL, Cohen JA, et al. Alemtuzumab has durable efficacy in relapsing-remitting multiple sclerosis patients: CARE-MS extension [abstract plus poster]. In: 7th World Congress on Controversies in Neurology; 11–14 Apr 2013; Istanbul.Google Scholar
- 32.LaGanke C, Arnold D, Cohen J, et al. Adverse event profile of alemtuzumab over time in active relapsing-remitting multiple sclerosis patients who experienced disease activity while on prior therapy (CARE-MS II) [abstract no. P01.174]. In: 65th Annual Meeting of the American Academy of Neurology; 16-23 Mar 2013; San Diego (CA).Google Scholar
- 33.Lycke J, Arnold D, Coles A, et al. Adverse event profile of alemtuzumab over time in treatment-naive patients with early, active relapsing-remitting multiple sclerosis (CARE-MS I study) [abstract no. P202 plus poster]. In: 21st World Congress of Neurology; 21–26 Sep 2013; Vienna.Google Scholar
- 34.Havrdova E, Arnold D, Cohen J, et al. Lymphocyte counts and infection risk among relapsing-remitting multiple sclerosis patients treated with alemtuzumab (CARE-MS II) [abstract no. P528]. J Neurol. 2013;260(Suppl. 1):S120.Google Scholar
- 37.Margolin D, Rizzo M, Smith G, et al. Alemtuzumab treatment has no adverse impact on sperm quality, quantity, or motility: a CARE-MS substudy [abstract no. P201 plus poster]. In: 21st World Congress of Neurology; 21–26 Sep 2013; Vienna.Google Scholar
- 38.Fox E, Arnold D, Cohen J, et al. Autoimmunity in patients treated with alemtuzumab for relapsing-remitting multiple sclerosis [abstract no. P1005]. In: 28th Congress of the European Committee for Treatment & Research in Multiple Sclerosis; 10–13 Oct 2012; Lyon.Google Scholar
- 39.Wynn D, Arnold D, Cohen J, et al. Detection, incidence and management of glomerulonephritis in the alemtuzumab clinical development programme [abstract no. P597]. In: 29th congress of the European Committee for Research and Treatment of Multiple Sclerosis; 2–5 Oct 2013; Copenhagen.Google Scholar
- 40.National Institute for Health and Care Excellence. Guidance in development: multiple sclerosis (2014). 2013. http://www.nice.org.uk/guidance/index.jsp?action=byID&o=13595. Accessed 4 Nov 2013.
- 41.National Institute for Health and Care Excellence. Multiple sclerosis (relapsing-remitting) - alemtuzumab [ID539]. 2013. http://guidance.nice.org.uk/index.jsp?action=byID&o=14060. Accessed 28 Jan 2014.
- 43.Genzyme. Genzyme receives complete response letter from FDA on Lemtrada™ (alemtuzumab) application. 2013. http://news.genzyme.com/press-release/genzyme-receives-complete-response-letter-fda-lemtrada-alemtuzumab-application. Accessed 7 Feb 2014.