Newer agents in the treatment of multiple sclerosis

Neurologist

Volumn 19, Issue 4, 2015, Pages 104-117

  Pawate, Siddharama ^a   Bagnato, Francesca ^b  

^a VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^b UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

Author keywords

demyelination; inflammation; multiple sclerosis; neuroprotection; treatment

Indexed keywords

ALEMTUZUMAB; DACLIZUMAB; FINGOLIMOD; FUMARIC ACID DIMETHYL ESTER; LAQUINIMOD; NATALIZUMAB; OCRELIZUMAB; OFATUMUMAB; RITUXIMAB; TERIFLUNOMIDE; CD20 ANTIGEN; CROTONIC ACID DERIVATIVE; MONOCLONAL ANTIBODY; TOLUIDINE DERIVATIVE;

AUTOIMMUNE THYROIDITIS; BRADYCARDIA; BRAIN EDEMA; BRONCHITIS; CLINICAL FEATURE; DIARRHEA; DRUG EFFICACY; FLUSHING; GASTROINTESTINAL SYMPTOM; GLOMERULOPATHY; HAIR DISEASE; HERPES SIMPLEX ENCEPHALITIS; HERPES ZOSTER; HUMAN; HYPERTRANSAMINASEMIA; IDIOPATHIC THROMBOCYTOPENIC PURPURA; INFECTION; INFUSION RELATED REACTION; MACULAR EDEMA; MULTIPLE SCLEROSIS; NAUSEA; NEUROPROTECTION; NUCLEAR MAGNETIC RESONANCE IMAGING; PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; REMYELINIZATION; REVIEW; SIDE EFFECT; CLINICAL TRIAL (TOPIC); IMMUNOLOGY; TREATMENT OUTCOME;

ANTIBODIES, MONOCLONAL; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTIGENS, CD20; CLINICAL TRIALS AS TOPIC; CROTONATES; DIMETHYL FUMARATE; FINGOLIMOD HYDROCHLORIDE; HUMANS; MULTIPLE SCLEROSIS; TOLUIDINES; TREATMENT OUTCOME;

EID: 84940840582     PISSN: 10747931     EISSN: None     Source Type: Journal    
DOI: 10.1097/NRL.0000000000000020     Document Type: Review

References (123)

1. Who gets MS? 2012. Available at: http: //www.nationalmssociety. org/about-multiple-sclerosis/what-we-know-about-ms/who-gets-ms/index.aspx
2. Pugliatti M., et al. The epidemiology of multiple sclerosis in Europe. Eur J Neurol. 2006; 13: 700-722
3. Bar-Or A. The immunology of multiple sclerosis. Semin Neurol. 2008; 28: 29-45
4. Kasper LH, Shoemaker J. Multiple sclerosis immunology: the healthy immune system vs the MS immune system. Neurology. 2010; 74(suppl 1): S2-S8
5. Sospedra M, Martin R. Immunology of multiple sclerosis. Annu Rev Immunol. 2005; 23: 683-747
6. Paty DW, Li DK. Interferon beta-1b is effective in relapsingremitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. UBC MS/MRI Study Group and the IFNB Multiple Sclerosis Study Group. Neurology. 1993; 43: 662-667
7. Interferon beta-1b in the treatment of multiple sclerosis: final outcome of the randomized controlled trial. The IFNB Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group. Neurology. 1995; 45: 1277-1285
8. Rudick RA. Betaseron for multiple sclerosis. Implications for therapeutics. Arch Neurol. 1994; 51: 125-128
9. Jacobs LD., et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol. 1996; 39: 285-294
10. Rudick RA., et al. Impact of interferon beta-1a on neurologic disability in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Neurology. 1997; 49: 358-363
11. Simon JH., et al. Magnetic resonance studies of intramuscular interferon beta-1a for relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group. Ann Neurol. 1998; 43: 79-87
12. Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet. 1998; 352: 1498-1504
13. Li DK, Paty DW. Magnetic resonance imaging results of the PRISMS trial: a randomized, double-blind, placebo-controlled study of interferon-beta1a in relapsing-remitting multiple sclerosis. Prevention of Relapses and Disability by Interferon-beta1a Subcutaneously in Multiple Sclerosis. Ann Neurol. 1999; 46: 197-206
14. Johnson KP., et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology. 1995; 45: 1268-1276
15. Polman CH., et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006; 354: 899-910
16. Rudick RA., et al. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med. 2006; 354: 911-923
17. Langer-Gould A., et al. Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med. 2005; 353: 375-381
18. Derfuss T, Kappos L. Predicting PML in natalizumab-treated patients: can we do better?. J Neurol Neurosurg Psychiatry. 2013; 84: 1182-1183
19. The TYSABRI TOUCH Prescribing Program. 2013. Available at: http: //www.tysabri.com/safety-with-tysabri.xml
20. Bloomgren G., et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012; 366: 1870-1880
21. Martinelli V., et al. Mitoxantrone: benefits and risks in multiple sclerosis patients. Neurol Sci. 2009; 30(suppl 2): S167-S170
22. Carter NJ, Keating GM. Glatiramer acetate: a review of its use in relapsing-remitting multiple sclerosis and in delaying the onset of clinically definite multiple sclerosis. Drugs. 2010; 70: 1545-1577
23. Plosker GL. Interferon-beta-1b: a review of its use in multiple sclerosis. CNS Drugs. 2011; 25: 67-88
24. Sanford M, Lyseng-Williamson KA. Subcutaneous recombinant interferon-beta-1a (Rebif(R)): a review of its use in the treatment of relapsing multiple sclerosis. Drugs. 2011; 71: 1865-1891
25. Keegan BM. Natalizumab for multiple sclerosis: a complicated treatment. Lancet Neurol. 2011; 10: 677-678
26. Pelletier D, Hafler DA. Fingolimod for multiple sclerosis. N Engl J Med. 2012; 366: 339-347
27. Bagnato F. Application of interferon beta-1b in multiple sclerosis. Eur Neurol Rev. 2011; 6: 36-44
28. Bagnato F, Pirko I. Novel agents and emerging treatment strategies in multiple sclerosis. What role for cladribine?. Clin Med Insights: Ther. 2011; 3: 425-439
29. Cohen JA., et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010; 362: 402-415
30. Kappos L., et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010; 362: 387-401
31. OConnor P., et al. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011; 365: 1293-1303
32. Gold R., et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012; 367: 1098-1107
33. Fox RJ., et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl JMed. 2012; 367: 1087-1097
34. Compston A, Coles A. Multiple sclerosis. Lancet. 2008; 372: 1502-1517
35. Courtney AM., et al. Multiple sclerosis. Med Clin North Am. 2009; 93: 451-476, ix-x.
36. Lublin FD., et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014; 83: 278-286
37. Frohman EM., et al. Characterizing the mechanisms of progression in multiple sclerosis: evidence and new hypotheses for future directions. Arch Neurol. 2005; 62: 1345-1356
38. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983; 33: 1444-1452
39. Cutter GR., et al. Development of a multiple sclerosis functional composite as a clinical trial outcome measure. Brain. 1999; 122(pt 5): 871-882
40. Bagnato F, Frank JA. The role of nonconventional magnetic resonance imaging techniques in demyelinating disorders. Curr Neurol Neurosci Rep. 2003; 3: 238-245
41. Bagnato F., et al. Evolution of T1 black holes in patients with multiple sclerosis imaged monthly for 4 years. Brain. 2003; 126(pt 8): 1782-1789
42. Miller DH., et al. Measurement of atrophy in multiple sclerosis: pathological basis, methodological aspects and clinical relevance. Brain. 2002; 125(pt 8): 1676-1695
43. Van Waesberghe JH., et al. Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability. Ann Neurol. 1999; 46: 747-754
44. Brinkmann V. FTY720 (fingolimod) in multiple sclerosis: therapeutic effects in the immune and the central nervous system. Br J Pharmacol. 2009; 158: 1173-1182
45. Chun J, Hartung HP. Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis. Clin Neuropharmacol. 2010; 33: 91-101
46. Ingwersen J., et al. Fingolimod in multiple sclerosis: mechanisms of action and clinical efficacy. Clin Immunol. 2012; 142: 15-24
47. Lee CW, Choi JW, Chun J. Neurological S1P signaling as an emerging mechanism of action of oral FTY720 (fingolimod) in multiple sclerosis. Arch Pharm Res. 2010; 33: 1567-1574
48. Choi JW., et al. FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor 1 (S1P1) modulation. Proc Natl Acad Sci U S A. 2011; 108: 751-756
49. Jackson SJ, Giovannoni G, Baker D. Fingolimod modulates microglial activation to augment markers of remyelination. J Neuroinflammation. 2011; 8: 76
50. Miron VE., et al. Cyclical and dose-dependent responses of adult human mature oligodendrocytes to fingolimod. Am J Pathol. 2008; 173: 1143-1152
51. Miron VE, Schubart A, Antel JP. Central nervous systemdirected effects of FTY720 (fingolimod). J Neurol Sci. 2008; 274: 13-17
52. Turaka K, Bryan Does JS. fingolimod in multiple sclerosis patients cause macular edema?. J Neurol. 2012; 259: 386-388
53. Jander S., et al. Emerging tumefactive multiple sclerosis after switching therapy from natalizumab to fingolimod. Mult Scler. 2012; 18: 1650-1652
54. Visser F., et al. Tumefactive multiple sclerosis lesions under fingolimod treatment. Neurology. 2012; 79: 2000-2003
55. Ferraro D., et al. Frequent early multiple sclerosis relapses during treatment with fingolimod: a paradoxical effect?. Mult Scler. 2013; 19: 1550
56. Kinney MO, McDonnell G. Re: Tumefactive multiple sclerosis lesions under fingolimod treatment. Neurology. 2013; 81: 403
57. Bourdette D, Gilden D. Fingolimod and multiple sclerosis: four cautionary tales. Neurology. 2012; 79: 1942-1943
58. Zarbin M.A., et al. Ophthalmic evaluations in clinical studies of fingolimod (FTY720) in multiple sclerosis. Ophthalmology. 2013; 120: 1432-1439
59. Ormerod AD, Mrowietz U. Fumaric acid esters, their place in the treatment of psoriasis. Br J Dermatol. 2004; 150: 630-632
60. Wilms H., et al. Dimethylfumarate inhibits microglial and astrocytic inflammation by suppressing the synthesis of nitric oxide, IL-1beta, TNF-alpha and IL-6 in an in-vitro model of brain inflammation. J Neuroinflammation. 2010; 7: 30
61. Wallbrecht K., et al. Downregulation of endothelial adhesion molecules by dimethylfumarate, but not monomethylfumarate, and impairment of dynamic lymphocyte-endothelial cell interactions. Exp Dermatol. 2011; 20: 980-985
62. Ghoreschi K., et al. Fumarates improve psoriasis and multiple sclerosis by inducing type II dendritic cells. J Exp Med. 2011; 208: 2291-2303
63. Gerdes S, Shakery K, Mrowietz U. Dimethylfumarate inhibits nuclear binding of nuclear factor kappaB but not of nuclear factor of activated T cells and CCAAT/enhancer binding protein beta in activated human T cells. Br J Dermatol. 2007; 156: 838-842
64. Seidel P., et al. Dimethylfumarate inhibits NF-{kappa}B function at multiple levels to limit airway smooth muscle cell cytokine secretion. Am J Physiol Lung Cell Mol Physiol. 2009; 297: L326-L339
65. Seidel P., et al. Inhibition of NF-kappaB and AP-1 by dimethylfumarate correlates with down-regulated IL-6 secretion and proliferation in human lung fibroblasts. Swiss Med Wkly. 2010; 140: w13132
66. Gesser B., et al. Dimethylfumarate specifically inhibits the mitogen and stress-activated kinases 1 and 2 (MSK1/2): possible role for its anti-psoriatic effect. J Invest Dermatol. 2007; 127: 2129-2137
67. Ashrafian H., et al. Fumarate is cardioprotective via activation of the Nrf2 antioxidant pathway. Cell Metab. 2012; 15: 361-371
68. Linker RA., et al. Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain. 2011; 134(pt 3): 678-692
69. Kaltwasser JP, Behrens F. Leflunomide: long-term clinical experience and new uses. Expert Opin Pharmacother. 2005; 6: 787-801
70. FDA approves new multiple sclerosis treatment Aubagio. 2012. Available at: http: //www.fda.gov/NewsEvents/Newsroom/Press-Announcements/ucm319277.htm
71. Greene S., et al. Inhibition of dihydroorotate dehydrogenase by the immunosuppressive agent leflunomide. Biochem Pharmacol. 1995; 50: 861-867
72. Vermersch P., et al. Teriflunomide versus subcutaneous interferon beta-1a in patients with relapsing multiple sclerosis: a randomised, controlled phase 3 trial. Mult Scler. 2014; 20: 705-716
73. Wolinsky JS., et al. Magnetic resonance imaging outcomes from a phase III trial of teriflunomide. Mult Scler. 2013; 19: 1310-1319
74. Warnke C., et al. Review of teriflunomide and its potential in the treatment of multiple sclerosis. Neuropsychiatr Dis Treat. 2009; 5: 333-340
75. Noseworthy JH., et al. Linomide in relapsing and secondary progressive MS: part I: trial design and clinical results. North American Linomide Investigators. Neurology. 2000; 54: 1726-1733
76. Wolinsky JS., et al. Linomide in relapsing and secondary progressive MS: part II: MRI results. MRI Analysis Center of the University of Texas-Houston, Health Science Center, and the North American Linomide Investigators. Neurology. 2000; 54: 1734-1741
77. Polman C., et al. Treatment with laquinimod reduces development of active MRI lesions in relapsing MS. Neurology. 2005; 64: 987-991
78. Bruck W, Wegner C. Insight into the mechanism of laquinimod action. J Neurol Sci. 2011; 306: 173-179
79. Vollmer TL., et al. A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis. J Neurol. 2014; 261: 773-783
80. Bates D. Alemtuzumab. Int MS J. 2009; 16: 75-76
81. Jones JL., et al. Improvement in disability after alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunity. Brain. 2010; 133(pt 8): 2232-2247
82. Coles AJ., et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008; 359: 1786-1801
83. Coles AJ., et al. Alemtuzumab more effective than interferon beta-1a at 5-year follow-up of CAMMS223 clinical trial. Neurology. 2012; 78: 1069-1078
84. Cohen JA., 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
85. Coles AJ., et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012; 380: 1829-1839
86. Lim SH., et al. Anti-CD20 monoclonal antibodies: historical and future perspectives. Haematologica. 2010; 95: 135-143
87. Bar-Or A., et al. Rituximab in relapsing-remitting multiple sclerosis: a 72-week, open-label, phase I trial. Ann Neurol. 2008; 63: 395-400
88. Hawker K., et al. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebocontrolled multicenter trial. Ann Neurol. 2009; 66: 460-471
89. Hauser SL., et al. B-cell depletion with rituximab in relapsingremitting multiple sclerosis. N Engl J Med. 2008; 358: 676-688
90. Naismith RT., et al. Rituximab add-on therapy for breakthrough relapsing multiple sclerosis: a 52-week phase II trial. Neurology. 2010; 74: 1860-1867
91. Hutas G. Ocrelizumab, a humanized monoclonal antibody against CD20 for inflammatory disorders and B-cell malignancies. Curr Opin Investig Drugs. 2008; 9: 1206-1215
92. Kappos L., et al. Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial Lancet. 2011; 378: 1779-1787
93. Sorensen PS., et al. Magnetic resonance imaging (MRI) efficacy of ofatumumab in relapsing-remitting multiple sclerosis (RRMS) -24-week results of a phase II study. Mult Scler. 2010; 16(suppl): S7-S39
94. Wynn D., et al. Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebocontrolled, add-on trial with interferon beta. Lancet Neurol. 2010; 9: 381-390
95. Hvardova E. Positive Proof of Concept of AIN457, an Antibody Against Interleukin-17A, in Relapsing-Remitting Multiple Sclerosis, in ECTRIMS. Lyons, France; 2012
96. Miller DH., et al. Firategrast for relapsing remitting multiple sclerosis: a phase 2, randomised, double-blind, placebocontrolled trial. Lancet Neurol. 2012; 11: 131-139
97. Stuve O., et al. Phase 2 BOLD Extension Study Efficacy Results for Siponimod (BAF312) in Patients with Relapsing-Remitting Multiple Sclerosis. in American Academy of Neurology. San Diego, CA; 2013
98. Komiya T., et al. Efficacy and immunomodulatory actions of ONO-4641, a novel selective agonist for sphingosine 1-phosphate receptors 1 and 5, in preclinical models of multiple sclerosis. Clin Exp Immunol. 2013; 171: 54-62
99. Barkhof F., et al. Ibudilast in relapsing-remitting multiple sclerosis: a neuroprotectant?. Neurology. 2010; 74: 1033-1040
100. Fox E., et al. A randomized clinical trial of autologous T-cell therapy in multiple sclerosis: subset analysis and implications for trial design. Mult Scler. 2012; 18: 843-852
101. Sriram S. Role of glial cells in innate immunity and their role in CNS demyelination. J Neuroimmunol. 2011; 239: 13-20
102. Vergo S., et al. Acid-sensing ion channel 1 is involved in both axonal injury and demyelination in multiple sclerosis and its animal model. Brain. 2011; 134(pt 2): 571-584
103. Arun T., et al. Targeting ASIC1 in primary progressive multiple sclerosis: evidence of neuroprotection with amiloride. Brain. 2013; 136(pt 1): 106-115
104. Jepson S., et al. Lingo-1, a transmembrane signaling protein, inhibits oligodendrocyte differentiation and myelination through intercellular self-interactions. J Biol Chem. 2012; 287: 22184-22195
105. Safety Study of BIIB033 in SubjectsWith Multiple Sclerosis. 2012. Available at: http: //clinicaltrials.gov/ct2/show/NCT01244139
106. Wang T., et al. The role of Nogo-A in neuroregeneration: a review. Brain Res Bull. 2012; 87: 499-503
107. Comi G. Induction vs. escalating therapy in multiple sclerosis: practical implications. Neurol Sci. 2008; 29(suppl 2): S253-S255
108. Freedman MS. Induction vs. escalation of therapy for relapsing multiple sclerosis: the evidence. Neurol Sci. 2008; 29(suppl 2): S250-S252
109. Rieckmann P. Concepts of induction and escalation therapy in multiple sclerosis. J Neurol Sci. 2009; 277(suppl 1): S42-S45
110. Edan G., et al. Mitoxantrone prior to interferon beta-1b in aggressive relapsing multiple sclerosis: a 3-year randomised trial. J Neurol Neurosurg Psychiatry. 2011; 82: 1344-1350
111. Le Page E., et al. Mitoxantrone as induction treatment in aggressive relapsing remitting multiple sclerosis: treatment response factors in a 5 year follow-up observational study of 100 consecutive patients. J Neurol Neurosurg Psychiatry. 2008; 79: 52-56
112. Vollmer T., et al. Glatiramer acetate after induction therapy with mitoxantrone in relapsing multiple sclerosis. Mult Scler. 2008; 14: 663-670
113. Zaffaroni M., et al. Induction and add-on therapy with mitoxantrone and interferon beta in multiple sclerosis. Neurol Sci. 2008; 29(suppl 2): S230-S232
114. Le Page E, Edan G. Long-term experience with induction treatment regimens in multiple sclerosis. J Neurol Sci. 2009; 277(suppl 1): S46-S49
115. Harrison DM., et al. Treatment of relapsing-remitting multiple sclerosis with high-dose cyclophosphamide induction followed by glatiramer acetate maintenance. Mult Scler. 2012; 18: 202-209
116. Killestein J., et al. Natalizumab drug holiday in multiple sclerosis: poorly tolerated. Ann Neurol. 2010; 68: 392-395
117. Kerbrat A., et al. Natalizumab and drug holiday in clinical practice: an observational study in very active relapsing remitting multiple sclerosis patients. J Neurol Sci. 2011; 308: 98-102
118. Heisen M., et al. Fingolimod reduces direct medical costs compared to natalizumab in patients with relapsing-remitting multiple sclerosis in The Netherlands. J Med Econ. 2012; 15: 1149-1158
119. Havla J., et al. Fingolimod reduces recurrence of disease activity after natalizumab withdrawal in multiple sclerosis. J Neurol. 2013; 260: 1382-1387
120. Centonze D., et al. Severe relapses under fingolimod treatment prescribed after natalizumab. Neurology. 2012; 79: 2004-2005
121. Daelman L., et al. Severe multiple sclerosis reactivation under fingolimod 3 months after natalizumab withdrawal. Mult Scler. 2012; 18: 1647-1649
122. Rinaldi F., et al. Switching therapy from natalizumab to fingolimod in relapsing-remitting multiple sclerosis: clinical and magnetic resonance imaging findings. Mult Scler. 2012; 18: 1640-1643
123. Sempere AP., et al. Switching from natalizumab to fingolimod: an observational study. Acta Neurol Scand. 2013; 128: e6-e10