Alemtuzumab – A New Efficacy Benchmark in Relapsing–Remitting Multiple Sclerosis? relapsing multiple sclerosis, N Engl J Med, 2006;354:899–910.

20. Cadavid D, Cheriyan J, Skurnick J, et al., New acute and chronic black holes in patients with multiple sclerosis randomised to interferon beta-1b or glatiramer acetate, J Neurol Neurosurg Psychiatry, 2009;80:1337–43.

21. Comi G, Martinelli V, Rodegher M, et al., Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial, Lancet, 2009;374:1503–11.

22. Mikol DD, Barkhof F, Chang P, et al., Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicentre, randomised, parallel, open-label trial, Lancet Neurol, 2008;7:903–14.

23. O'Connor P, Filippi M, Arnason B, et al., 250 microg or 500 microg interferon beta-1b versus 20mg glatiramer acetate in relapsing-remitting multiple sclerosis: a prospective, randomised, multicentre study, Lancet Neurol, 2009;8:889–97.

24. Schwid SR, Thorpe J, Sharief M, et al., Enhanced benefit of increasing interferon beta-1a dose and frequency in relapsing multiple sclerosis: the EVIDENCE Study, Arch Neurol, 2005;62:785–92.

25. Panitch H, Goodin D, Francis G, et al., Benefits of high-dose, high-frequency interferon beta-1a in relapsing-remitting multiple sclerosis are sustained to 16 months: final comparative results of the EVIDENCE trial, J Neurol Sci, 2005;239:67–74.

26. Durelli L, Verdun E, Barbero P, et al., Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis: results of a 2-year prospective randomised multicentre study (INCOMIN), Lancet, 2002;359:1453–60.

27. Deisenhammer F, Neutralizing antibodies to interferon-beta and other immunological treatments for multiple sclerosis: prevalence and impact on outcomes, CNS Drugs, 2009;23:379–96.

28. Goodin DS, Frohman EM, Hurwitz B, et al., Neutralizing antibodies to interferon beta: assessment of their clinical and radiographic impact: an evidence report: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology, Neurology, 2007;68:977–84.

29. Hartung HP, Munschauer F III, Schellekens H, Significance of neutralizing antibodies to interferon beta during treatment of multiple sclerosis: expert opinions based on the Proceedings of an International Consensus Conference, Eur J Neurol, 2005;12:588–601.

30. Koch-Henriksen N, Sorensen PS, Bendtzen K, et al., The clinical effect of neutralizing antibodies against interferon- beta is independent of the type of interferon-beta used for patients with relapsing-remitting multiple sclerosis, Mult Scler, 2009;15:601–5.

31. Pachner AR, Warth JD, Pace A, et al., Effect of neutralizing antibodies on biomarker responses to interferon beta: the INSIGHT study, Neurology, 2009;73:1493–1500.

32. van der Voort LF, Gilli F, Bertolotto A, et al., Clinical effect of neutralizing antibodies to interferon beta that persist long after cessation of therapy for multiple sclerosis, Arch Neurol, 2010;67:402–7.

33. Wiendl H, Toyka KV, Rieckmann P, et al., Basic and escalating immunomodulatory treatments in multiple sclerosis: current therapeutic recommendations, J Neurol, 2008;255:1449–63.

34. Belachew S, Phan-Ba R, Bartholome E, et al., Natalizumab induces a rapid improvement of disability status and ambulation after failure of previous therapy in relapsing- remitting multiple sclerosis, Eur J Neurol, 2010 (Epub ahead of print).

35. Coyle PK, The role of natalizumab in the treatment of multiple sclerosis, Am J Manag Care, 2010;16:S164–70.

36. Kleinschmidt-DeMasters BK, Tyler KL, Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis, N Engl J Med, 2005;353:369–74.

37. Langer-Gould A, Atlas SW, Green AJ, et al., Progressive multifocal leukoencephalopathy in a patient treated with natalizumab, N Engl J Med, 2005;353:375–81.

38. Yousry TA, Major EO, Ryschkewitsch C, et al., Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy, N Engl J Med, 2006;354:924–33.

39. Subramanyam M, Plavina T, Simon K, et al., Factors associated with anti-JCV antibody prevalence in a large cohort of natalizumab-treated MS patients. 26th Congress of the European Committee for Treatment and Research in Multiple Sclerosis. P138, Gothenberg, Sweden, 13–16 October 2010.

40. Ghalie RG, Edan G, Laurent M, et al., Cardiac adverse effects associated with mitoxantrone (Novantrone) therapy in patients with MS, Neurology, 2002;59:909–13.

41. Martinelli V, Incidence of Acute Leukaemia in Multiple Sclerosis Patients Treated with Mitoxandrone: A Multicentre Retrospective Italian Study. Abstract from the 61st Annual Meeting of the American Academy of Neurology (AAN), Seattle, WA, 2009.

42. Rammohan KW, Shoemaker J, Emerging multiple sclerosis oral therapies, Neurology, 2010;74(Suppl. 1):S47–53.

43. Patti F, Optimizing the benefit of multiple sclerosis therapy: the importance of treatment adherence, Patient Prefer Adherence, 2010;4:1–9.

44. Turner AP, Williams RM, Sloan AP, et al., Injection anxiety remains a long-term barrier to medication adherence in multiple sclerosis, Rehabil Psychol, 2009;54:116–21.

45. Comi G, Pulizzi A, Rovaris M, et al., Effect of laquinimod on MRI-monitored disease activity in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study, Lancet, 2008;371:2085–92.

46. Conway D, Cohen JA, Emerging Oral Therapies in Multiple Sclerosis, Curr Neurol Neurosci Rep, 2010;10(5):381–8.

47. Giovannoni G, Comi G, Cook S, et al., A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis, N Engl J Med, 2010;362:416–26.

48. Kappos L, Gold R, Miller DH, et al., Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study, Lancet, 2008;372: 1463–72.

49. Marriott JJ, O'Connor PW, Emerging Therapies in Relapsing-Remitting Multiple Sclerosis, Rev Recent Clin Trials, 2010;5(3):179–88.

50. O'Connor P, Wolinsky J, Confavreux C, et al., A placebo-controlled phase III trial (TEMSO) of oral teriflunomide in relapsing multiple sclerosis: clinical efficacy and safety outcomes. 26th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), Gothenberg, Sweden, 13–16 October 2010.

51. Buttmann M, Treating multiple sclerosis with monoclonal antibodies: a 2010 update, Expert Rev Neurother, 2010;10: 791–809.

52. Demko S, Summers J, Keegan P, et al., FDA drug approval summary: alemtuzumab as single-agent treatment for B-cell chronic lymphocytic leukemia, Oncologist, 2008;13: 167–74.

53. Jones JL, Coles AJ, Spotlight on alemtuzumab, Int MS J, 2009;16:77–81.

54. Jones JL, Anderson JM, Phuah CL, et al., Improvement in disability after alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunity, Brain, 2010;133(Pt 8):2232–47.

55. Xia MQ, Tone M, Packman L, et al., Characterization of the CAMPATH-1 (CDw52) antigen: biochemical analysis and cDNA cloning reveal an unusually small peptide backbone, Eur J Immunol, 1991;21:1677–84.

56. Simpson BS, Coles AJ, Rationale for cytotoxic monoclonal antibodies in MS, Int MS J, 2007;14:48–56.

57. Gilleece MH, Dexter TM, Effect of Campath-1H antibody on human hematopoietic progenitors in vitro, Blood, 1993;82:807–12.

58. 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;128:260–70.

59. Cox AL, Thompson SA, Jones JL, et al., Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis, Eur J Immunol, 2005;35:3332–42.

60. Thompson SA, Jones JL, Cox AL, et al., B-cell reconstitution and BAFF after alemtuzumab (Campath-1H) treatment of multiple sclerosis, J Clin Immunol, 2010;30:99–105.

61. Coles AJ, Cox A, Le Page E, et al., The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy, J Neurol, 2006;253:98-108.

62. The CAMMS223 Trial Investigators, Alemtuzumab vs. interferon beta-1a in early multiple sclerosis, N Engl J Med, 2008;359:1786–801.

63. Coles A on behalf of the CAMMS223 Study Group, Alemtuzumab treatment benefit is durable: primary efficacy outcomes of CAMMS223 at 4 years Presented at the 25TH Congress of the European Committee for Treatment and Research in Multiple Sclerosis, Dusseldorf, Germany, 9–12 September 2009, Poster P 890.

64. Khan O on Behalf of the CAMMS223 Study Group, Alemtuzumab Reduces Disease Progression in RRMS: Long-Term Results of the CAMMS223 Trial, presented at the 62nd Annual meeting of the American Society of Neurology, Toronto, Canada, 12–17 April 2010, Poster P04.213.

65. Fox E on Behalf of the CAMMS223 Study Group, Long-Term Follow-Up of Immune Thrombocytopenia after Treatment of Multiple Sclerosis Patients with Alemtuzumab in CAMMS223, Presented at the 62nd Annual meeting of the American Society of Neurology, Toronto, Canada, 12–17 April 2010, P05.036.

66. Brinar V on Behalf of the CAMMS223 Study Group, Benefits of Alemtuzumab Are Evident Even in Relapsing- Remitting Multiple Sclerosis Patients Who Experience Autoimmune Adverse Events, Presented at the 62nd Annual meeting of the American Society of Neurology, Toronto, Canada, 12–17 April 2010, P03.114.

67. Meyer D, Coles A on behalf of the CAMMS223 Study Group, Case report of anti-glomerular basement membrane disease following alemtuzumab treatment, 26th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), 13–16 September 2010 Gothenberg, Sweden 2010.

68. Jones JL, Phuah CL, Cox AL, et al., IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H), J Clin Invest, 2009;119:2052–61.

69. Clatworthy MR, Wallin EF, Jayne DR, Anti-glomerular basement membrane disease after alemtuzumab, N Engl J Med, 2008;359:768–9.

70. Havrdova E for the Care-MS Steering Committee. The CARE-MS I trial (Comparison of Alemtuzumab and Rebif Efficacy in multiple sclerosis): design of a Phase 3, open-label, rater-blinded study of alemtuzumab in treatment-naive patients with relapsing MS. 60th Annual meeting of the American academy of Neurology, Chicago, USA, 2008.

71. Fox E for the CARE-MS Steering Committee. The CARE-MS II trial (Comparison of Alemtuzumab and rebif Efficacy in multiple sclerosis): design of a Phase 3, open-label, rater-blinded study of alemtuzumab in treatment-naive patients who have relapsed on therapy. 60th Annual meeting of the American academy of Neurology, Chicago, USA, 2008.

72. LaGanke C on behalf of the the CAMMS Study Groups. CARE-MS extension study: as needed RRMS treatment paradigm with alemtuzumab. 24th Annual meeting of the Consortium of Multiple Sclerosis Centers, San Antonio, USA, 2–5 June 2010.

73. Boster A, Edan G, Frohman E, et al., Intense immunosuppression in patients with rapidly worsening multiple sclerosis: treatment guidelines for the clinician, Lancet Neurol, 2008;7:173–83.

74. Harris VK, Sadiq SA, Disease biomarkers in multiple sclerosis: potential for use in therapeutic decision making, Mol Diagn Ther, 2009;13:225–44.

75. Hauser SL, Waubant E, Arnold DL, et al., B-cell depletion with rituximab in relapsing-remitting multiple sclerosis, N Engl J Med, 2008;358:676–88.

76. Wynn D, Kaufman M, Montalban X, et al., Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta, Lancet Neurol, 2010;9:381–90.

EUROPEAN NEUROLOGICAL REVIEW

89