Alemtuzumab: A Place in Therapy for Treatment of Multiple Sclerosis


Alemtuzumab is a humanized mononclonal antibody known to cause rapid depletion of B-and T-cell lymphocytes. Subsequent repletion of these lymphocytes leads to changes in adaptive immunity. Alemtuzumab is approved by the United States Food and Drug Administration (FDA) for the treatment of B-cell lymphocytic leukemia but has been investigated off-label in recent years for treatment of autoimmune diseases, including multiple sclerosis (MS). In MS treatment, alemtuzumab is administered as pulsed therapy, given once daily initially for 5 consecutive days and then for 3 consecutive days at 12-month intervals. Alemtuzumab has recently been compared to interferon beta 1-a in one phase II and two phase III trials in patients with relapsing-remitting MS. Results from the studies show alemtuzumab compared to interferon beta 1-a is associated with a greater reduction in the risk of sustained accumulation of disability and is more effective in reducing disease relapse rates. The treatment of MS continues to be a healthcare challenge due to the modest clinical benefit and adverse effect profiles of available disease modifying treatment options. Available data suggest alemtuzumab may offer better efficacy outcomes compared to traditional disease modifying therapies in patients with MS. However, the agent has not been compared to other new disease modifying medications that have been recently introduced.

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T. Tietje, D. Allington and M. Rivey, "Alemtuzumab: A Place in Therapy for Treatment of Multiple Sclerosis," International Journal of Clinical Medicine, Vol. 4 No. 10, 2013, pp. 459-471. doi: 10.4236/ijcm.2013.410082.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] R. L. Talbert, J. T. DiPiro, G. R. Matzke, L. M. Posey, B. G. Wells and G. C. Yee, “Multiple Sclerosis,” In: R. L Talbert, J. T. DiPiro, G. R. Matzke, L. M. Posey, B. G. Wells and G. C. Yee (Eds.), Pharmacotherapy: A Pathophysiologic Approach, 8e.
[2] J. Noseworthy, C. Lucchinetti, M. Rodriguez and B. Weinshenker, “Multiple Sclerosis,” The New England Journal of Medicine, Vol. 343, No. 13, 2000, pp. 938-952.
[3] C. Polman, S. Reingold, B. Banwell, M. Clanet, J. A. Cohen, M. Filippi, K. Fujihara, E. Havrdova, M. Hutchinson, L. Kappos, F. D. Lublin, X. Montalban, P. O’Connor, M. Sandberg-Wollheim, A. J. Thompson, E. Waubant, B. Weinshenker and J. S. Wolinsky, “Diagnostic Criteria for Multiple Sclerosis: 2010 Revisions to the Mcdonald Criteria,” Annals of Neurology, Vol. 69, No. 2, 2011, pp. 292-302.
[4] E. Zintzaras, C. Doxani, T. Mprotsis, C. Schmid and G. Hadjigeorgiou, “Network Analysis of Randomized Controlled Trials in Multiple Sclerosis,” Clinical Therapeutics, Vol. 34, No. 4, 2012, pp. 857-869.
[5] M. Pugliatti, S. Sotgiu and G. Rosati, “The Worldwide Prevalence of Multiple Sclerosis,” Clinical Neurology and Neurosurgery, Vol. 104, No. 3, 2002, pp. 182-191.
[6] G. Rosati, “The Prevalence of Multiple Sclerosis in the World: An Update,” Neurological Sciences, Vol. 22, No. 2, 2001, pp. 117-139.
[7] G. Dean, H. McLoughlin, R. Brady, A. Adelstein and J. Tallett-William, “Multiple Sclerosis among Immigrants in Greater London,” British Medical Journal, Vol. 1, No. 6014, 1976, pp. 861-864.
[8] B. Visscher, R. Detels, A. Coulson, R. Malmgren and J. Dudley, “Latitude, Migration and the Prevalence of Multiple Sclerosis,” American Journal of Epidemiology, Vol. 106, No. 6, 1977, pp. 470-475.
[9] C. Gale and C. Martyn, “Migrant Studies in Multiple Sclerosis,” Progress in Neurobiology, Vol. 47, No. 4-5, 1995, pp. 425-448.
[10] R. Marrie, “Environmental Risk Factors in Multiple Sclerosis Aetiology,” Lancet, Vol. 3, No. 12, 2004, pp. 709-718.
[11] A. Ascherio, K. Munger, E. Lenette, D. Spiegelman, M. A. Hernán, M. J. Olek, S. E. Hankinson and D. J. Hunter, “Epstein-Barr Virus Antibodies and Risk of Multiple Sclerosis: A Prospective Study,” Journal of the American Medical Association, Vol. 286, No. 24, 2001, pp. 3083-3088.
[12] R. Marrie and C. Wolfson, “Multiple Sclerosis and Epstein-Barr Virus,” Canadian Journal of Infectious Diseases, Vol. 13, No. 2, 2002, pp. 111-118.
[13] B. Serafini, L. Muzio, B. Rosicarelli and A. Francesca, “Radioactive in Situ Hybridization for Epstein-Barr Virus-Encoded Small RNA Supports Presence of Epstein-Barr Virus in the Multiple Sclerosis Brain,” Brain, Vol. 136, No. 7, 2013, p. e233.
[14] R. Magliozzi, B. Serafini, B. Rosicarelli, B. Chiappetta, C. Veroni, R. Reynolds and F. Alosi, “B-Cell Enrichment and Epstein-Barr Virus Infection in Inflammatory Cortical Lesions in Secondary Progressive Multiple Sclerosis,” Journal of Neuropathology & Experimental Neurology, Vol. 72, No. 1, 2013, pp. 29-41.
[15] L. Levin, K. Munger, M. Rubertone, C. A. Peck, E. T. Lennette, D. Spiegelman and A. Ascherio, “Temporal Relationship between Elevation of Epstein-Barr Virus Antibody Titers and Initial Onset of Neurological Symptoms in Multiple Sclerosis,” Journal of the American Medical Association, Vol. 239, No. 20, 2005, pp. 2496-2500.
[16] P. Challoner, K. Smith, J. Parker, D. L. MacLeod, S. N. Coulter, T. M. Rose, E. R. Schultz, J. L. Bennett, R. L. Garber and M. Chang, “Plaque-Associated Expression of Human Herpesvirus 6 in Multiple Sclerosis,” Proceedings of the National Academy of Sciences, Vol. 92, No. 16, 1995, pp. 7440-7444.
[17] J. Pietilainen, J. Virtanen, L. Uotila, L. Saloned, M. Koskiniemi and M. Farkkila, “HHV-6 Infection in Multiple Sclerosis. A Clinical and Laboratory Analysis,” European Journal of Neurology, Vol. 17, No. 3, 2010, pp. 506-509.
[18] S. Simpson, B. Taylor, D. Dwyer, J. Taylor, L. Blizzard, A. L. Ponsonby, F. Pittas, T. Dwyer and l. van der Mei, “Anti-HHV-6 IgG Titer Significantly Predicts Subsequent Relapse Risk in Multiple Sclerosis,” Multiple Sclerosis Journal, Vol. 18, No. 6, 2012, pp. 799-806.
[19] N. Summerday, S. Brown, D. Allington and M. Rivey, “Vitamin D and Multiple Sclerosis: Review of a Possible Association,” Journal of Pharmacy Practice, Vol. 25, No. 1, 2011, pp. 75-84.
[20] G. Ebers, “Environmental Factors and Multiple Sclerosis,” Lancet Neurology, Vol. 7, No. 3, 2008, pp. 268-277.
[21] N. Robertson, J. O’Riordan, J. Chataway, D. P. Kingsley, D. H. Miller, D. Clayton and D. A. Compston, “Offspring Recurrence Rates and Clinical Characteristics of Conjugal Multiple Sclerosis,” Lancet, Vol. 349, No. 9065, 1997, pp. 1587-1590.
[22] G. Ebers, I. Yee, A. Sadavnick, P. Duquette and the Canadian Collaborative Study Group, “Conjugal Multiple Sclerosis Population-Based Prevalence and Recurrence Risks in Offspring,” Annals of Neurology, Vol. 48. No. 6, 2000, pp. 927-931.<927::AID-ANA14>3.0.CO;2-F
[23] G. Ebers, D. Bulman, A. Sadovnick, D. W. Paty, S. Warren, W. Hader, T. J. Murray, T. P. Seland, P. Duquette, T. Grey, R. Nelson, M. Nicolle and D. Brunet, “A Population-Based Study of Multiple Sclerosis in Twins,” The New England Journal of Medicine, Vol. 315, No. 26 1986, pp. 1638-1642.
[24] A. Sadovnick, H. Armstrong, G. Rice, D. Bulman, L. Hashimoto, D. W. Paty, S. A. Hashimoto, S. Warren, W. Hader, T. J. Murray, et al., “A Population-Based Study of Multiple Sclerosis in Twins: Update,” Annals of Neurology, Vol. 33, No. 3, 1993, pp. 281-285.
[25] M. H. Barnett and J. W. Prineas, “Relapsing and Remitting Multiple Sclerosis: Pathology of the Newly Forming Lesion,” Annals of Neurology, Vol. 55, No. 4, 2004, pp. 458-468.
[26] R. Gold, C. Linington and H. Lassmann, “Understanding Pathogenesis and Therapy of Multiple Sclerosis via Animal Models: 70 Years of Merits and Culprits in Experimental Autoimmune Encephalomyelitis Research,” Brain, Vol. 129, No. 8, 2006, pp. 1953-1971.
[27] F. W. Gay, T. J. Drye, G. W. Dick and M. M. Esiri, “The Application of Multifactorial Cluster Analysis in the Staging of Plaques in Early Multiple Sclerosis. Identification and Characterization of the Primary Demyelinating Lesion,” Brain, Vol. 120, No. 8, 1997, pp. 1461-1483.
[28] H. Lassmann, W. Brück and C. F. Lucchinetti, “The Immunopathology of Multiple Sclerosis: An Overview,” Brain Pathology, Vol. 17, No. 2, 2007, pp. 210-218.
[29] C. F. Luchinetti, W. Brück, J. Parisi, B. Scheithauer, M. Rodriquez and H. Lassman, “Heterogeneity of Multiple Sclerosis Lesions: Implications for the Pathogenesis of Demyelination,” Annals of Neurology, Vol. 47, No. 6, 2000, pp. 707-717.<707::AID-ANA3>3.0.CO;2-Q
[30] R. C. Selter and B. Hemmer, “Update on Immunopathogenesis and Immunotherapy in Multiple Sclerosis,” Immunotargets and Therapy, Vol. 2, 2013, pp. 21-30.
[31] J. W. Peterson, L. Bo, S. Mork, A. Chang, R. M. Ransohoff and B. D. Trapp,“VCAM-1 Positive Microglia Target Oligodendrocytes at the Border of Multiple Sclerosis Lesions,” Journal of Neuropathology & Experimental Neurology, Vol. 61, No. 6, 2002, pp. 539-546.
[32] A. Minagar and J. S. Alexander, “Blood-Brain Barrier Disruption in Multiple Sclerosis,” Multiple Sclerosis, Vol. 9, No. 3, 2003, pp. 540-549.
[33] D. M. Wingerchuk, C. F. Lucchinetti and J. H. Noseworthy, “Multiple Sclerosis: Current Pathophysiological Concepts,” Laboratory Investigation, Vol. 81, No. 3, 2001, pp. 263-281.
[34] H. Waldmann and G. Hale, “CAMPATH: From Concept to Clinic,” Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 360, No. 1461, 2005, pp. 1707-1711.
[35] D. Gómez-Almagues, M. Solano-Genesta, L. Tarín-Arzaga, J. L. Herrera-Garza, O. G. Cantú-Rodríguez, C. H. Gutiérrez-Aguirre and J. C. Jaime-Pérez, “Low-Dose Rituximab and Alemtuzumab Combination Therapy for Patients with Steroid-Refractory Autoimmune Cytopenias,” Blood, Vol. 116, No. 23, 2010, pp. 4783-4785.
[36] E. J. Fox, H. C. Sullivan, S. K. Gazda, L. Mayer, L. O’Donnell, K. Melia and S. L. Lake, “A Single-Arm, Open-Label Study of Alemtuzumab in Treatment-Refractory Patients With Multiple Sclerosis,” European Journal of Neurology, Vol. 19, No. 2, 2012, pp. 307-311.
[37] L. Klotz, S. Meuth and H. Wiendl, “Immune Mechanisms of New Therapeutic Strategies in Multiple Sclerosis—A Focus on Alemtuzumab,” Clinical Immunology, Vol. 142, No. 1, 2012, pp. 24-30.
[38] B. Bielekova and B. Becker, “Monoclonal Antibodies in MS: Mechanism of Action,” Neurology, Vol. 74, No. S1, 2010, pp. S31-S40.
[39] S. Rodig, J. Abramson, G. Pinkus, S. P. Treon, D. M. Dorfman, H. Y. Dong, M. A. Shipp and J. L. Kutok, “Heterogeneous CD52 Expression among Hematologic Neoplasm: Implications for the Use of Alemtuzumab (CAM-PATH-1H),” Clinical Cancer Research, Vol. 12, No. 23, 2006, pp. 7174-7179.
[40] A. Minagar, S. Alexander, A. Sahraian and R. Zivadinov, “Alemtuzumab and Multiple Sclerosis: Therapeutic Application,” Expert Opinion on Biological Therapy, Vol. 10, No. 3, 2010, pp. 421-429.
[41] J. L. Bennett and O. Stuve, “Update on Inflammation, Neurodegeneration, and Immunoregulation in Multiple Sclerosis: Therapeutic Implication,” Clinical Neuropharmacology, Vol. 32, No. 3, 2009, pp. 121-132.
[42] M. Klabusay, V. Sukova, P. Coupek, Y. Brychtova and J. Mayer, “Different Levels of CD52 Antigen Expression Evaluated by Quantitative Fluorescence Cytometry Are Detected on B-lymphocytes, CD34+ Cells and Tumor Cells of Patients With Chronic B-cell Lymphoproliferative Diseases,” Cytometry, Vol. 72, No. 5, 2007, pp. 363-370.
[43] T. Elter, I. Molnar, J. Kuhlmann, M. Hallek and C. Wendtner, “Pharmacokinetics of Alemtuzumab and the Relevance in Clinical Practice,” Leuk Lymphoma, Vol. 49, No. 12, 2008, pp. 2256-2262.
[44] D. R. Mould, A. Baumann, J. Kuhlmann, M. J. Keating,S. Weitman, P. Hillmen, L. R. Brettman, S. Reif and P. L. Bonate, “Population Pharmacokinetics-Pharmacodynamics of Alemtuzumab (CampathR) in Patients With Chronic Lymphocytic Leukaemia and its Link to Treatment Response,” British Journal of Clinical Pharmacology, Vol. 64, No. 3, 2007, pp. 278-291.
[45] P. Rebello, K. Cwynarski, M. Varughese, A. Eades, J. F. Apperley and G. Hale, “Pharmacokinetics of CAMPATH-1H in BMT Patients,” Cytotherapy, Vol. 3, No. 4, 2001, pp. 261-267.
[46] J. D. Isaacs, V. K. Manna, N. Rapson, K. J. Bulpitt, B. L. Hazleman, E. L. Matteson, E. W. St.Clair, T. J. Schnitzer and J. M. Johnston, “Campath-1H in Rheumatoid Arthritis—An Intravenous Dose-Ranging Study,” British Journal of Rheumatology, Vol. 35, No. 3, 1996, pp. 131-140.
[47] G. Hale, P. Rebello, L. R. Brettman, C. Fegan, B. Kennedy, E. Kimby, M. Leach, J. Lundin, H. Mellstedt, P. Moreton, A. C. Rawstron, H. Waldmann, A. Osterborg and P. Hillmen, “Blood Concentrations of Alemtuzumab and Antiglobulin Responses in Patients With Chronic Lymphocytic Leukemia Following Intravenous or Subcutaneous Routes of Administration,” Blood, Vol. 104, No. 4, 2004, pp. 948-955.
[48] G. A. Hill-Cawthorne, T. Button, O. Tuohy, J. L. Jones, K. May, J. Somerfield, A. Green, G. Giovannoni, D. A. S. Compston, M. T. Fahey and A. J. Coles, “Long Term Lymphocyte Reconstitution after Alemtuzumab Treatment of Multiple Sclerosis,” Journal of Neurology, Neurosurgery, and Psychiatry, Vol. 83, No. 3, 2012, pp. 298-304.
[49] A. J. Coles, D. A. Compston, K. W. Selmaj, S. L. Lake, S. Moran, D. H. Margolin, K. Norris and P. K. Tandon, “Alemtuzumab vs. Interferon Beta-1a in Early Multiple Sclerosis,” The New England Journal of Medicine, Vol. 359, No. 17, 2008, pp. 1786-1801.
[50] J. A. Cohen, A. J. Coles, D. L. Arnold, C. Confavreux, E. J. Fox, H. P. Hartung, E. Havrdova, K. W. Selmaj, H. L. Weiner, E. Fisher, W. Brinar, G. Giovannoni, M. Stojanovic, B. I. Ertik, S. L. Lake, D. H. Margolin, M. A. Panzara and D. A. Compston, “Alemtuzumab Versus Interferon Beta 1a as First-Line Treatment For Patients With Relapsing-Remitting Multiple Sclerosis: A Randomized Controlled Phase 3 Trial,” Lancet, Vol. 380, No. 9856, 2012, pp. 1819-1828.
[51] A. J. Coles,C. L. Twyman, D. L. Arnold, J. A. Cohen, C. Confavreux, E. J. Fox, H. P. Hartung, E. Havrdova, K. W. Selmaj, H. L. Weiner, T. Miller, E. Fisher, R. Sandbrink, S. L. Lake, D. H. Margolin, P. Oyuela, M. A. Panzara and D. A. Compston, “Alemtuzumab for Patients With Relapsing Multiple Sclerosis after Disease-Modifying Therapy: A Randomized Controlled Phase 3 Trial,” Lancet, Vol. 380, No. 9856, 2012, pp. 1829-1839.
[52] A. J. Coles, A. Cox, E. Le Page, J. Jones, S. A. Trip, J. Deans, S. Seaman, D. H. Miller, G. Hale, H. Waldmann and D. A. Compston, “The Window of Therapeutic Opportunity in Multiple Sclerosis: Evidence From Monoclonal Antibody Therapy,” Journal of Neurology, Vol. 253, No. 1, 2006, pp. 98-108.
[53] C. Hirst, A. Pace, T. Pickersgill, R. Jones, B. N. McLean, J. P. Zajicek, N. J. Scolding and N. P. Robetrson, “Campath 1-H Treatment in Patients With Aggressive Relapsing Remitting Multiple Sclerosis,” Journal of Neurology, Vol. 255, No. 2, 2008, pp. 231-238.
[54] A. J. Coles, E. Fox, A. Vladic,S. K. Gazda, V. Brinar, K. W. Selmaj, A. Skoromets, I. Stolyarov, A. Bass, H. Sullivan, D. H. Margolin, S. L. Lake, S. Moran, J. Palmer, M. S. Smith and D. A. Compston, “Alemtuzumab More Effective Than Interferon β-1a at 5-Year Follow-Up of CAMMS223 Clinical Trial,” Journal of Neurology, Vol. 78, No. 14, 2012, pp. 1069-1078.
[55] S. Krieger, D. Arnold, J. Cohen, A. J. Coles, C. Confavreux, E. J. Fox, H. Hartung, E. Havrdova, K. Selmaj, H. L. Weiner, T. A.Miller, C. L. Twyman, S. L. Lake, D. H. Margolin, M. A. Panzara and A. Compston, “Alemtuzumab is Efficacious in Highly-Active RRMS Patients in CARE-MS II,” 2013.
[56] J. L. Jones, C. Phuah, A. L. Cox, S. A. Thompson, M. Ban, J. Shawcross, A. Walton, S. J. Sawcer, A. Compston and A. J. Coles, “IL-21 Drives Secondary Autoimmunity in Patients With Multiple Sclerosis, Following Therapeutic Lymphocyte Depletion With Alemtuzumab (Campath— 1H),” Journal of Clinical Investigation, Vol. 119, No. 7, 2009, pp. 2052-2061.
[57] L. Costelloe, J. Jones and A. Coles, “Secondary Autoimmune Diseases Following Alemtuzumab Therapy for Multiple Sclerosis,” Expert Review of Neurotherapeutics, Vol. 12, No. 3, 2012, pp. 333-341.
[58] Alemtuzumab, “Millennium and ILEX Partners,” 2001.
[59] S. Jeffrey, “Lemtrada Gets Positive Opinion from European CHMP in MS,” 2013.
[60] “European Commission Approves Genzyme’s Multiple Sclerosis Treatment LemtradaTM (alemtuzumab),” 2013.

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