A changing treatment landscape for multiple sclerosis: Challenges and opportunities

Journal of Internal Medicine

Volumn 275, Issue 4, 2014, Pages 364-381

  Piehl, F ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

Author keywords

Biological therapies; Immunomodulatory therapy; Multiple sclerosis; Randomized controlled trial

Indexed keywords

ALEMTUZUMAB; BETA1A INTERFERON; DACLIZUMAB; FINGOLIMOD; FUMARIC ACID DIMETHYL ESTER; GLATIRAMER; INTERFERON BETA SERINE; LAQUINIMOD; NATALIZUMAB; NERVENTRA; OCRELIZUMAB; TERIFLUNOMIDE; UNCLASSIFIED DRUG;

DISEASE ACTIVITY; FOLLOW UP; HUMAN; MULTIPLE SCLEROSIS; PRIORITY JOURNAL; REVIEW;

BIOLOGICAL THERAPIES; IMMUNOMODULATORY THERAPY; MULTIPLE SCLEROSIS; RANDOMIZED CONTROLLED TRIAL;

ADJUVANTS, IMMUNOLOGIC; ANTIBODIES, MONOCLONAL; CLINICAL TRIALS AS TOPIC; EVIDENCE-BASED MEDICINE; HUMANS; IMMUNOLOGIC FACTORS; IMMUNOSUPPRESSIVE AGENTS; MONITORING, PHYSIOLOGIC; MULTIPLE SCLEROSIS; TREATMENT OUTCOME;

EID: 84897025098     PISSN: 09546820     EISSN: 13652796     Source Type: Journal    
DOI: 10.1111/joim.12204     Document Type: Review

References (88)

1. Compston A, Coles A. Multiple sclerosis. Lancet 2008; 372: 1502-17.
2. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69: 292-302.
3. Miller D, Barkhof F, Montalban X, Thompson A, Filippi M. Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis. Lancet Neurol 2005; 4: 281-8.
4. Sawcer S, Hellenthal G, Pirinen M, et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011; 476: 214-9.
5. Handel AE, Giovannoni G, Ebers GC, Ramagopalan SV. Environmental factors and their timing in adult-onset multiple sclerosis. Nat Rev Neurol 2010; 6: 156-66.
6. Hedstrom AK, Sundqvist E, Baarnhielm M, et al. Smoking and two human leukocyte antigen genes interact to increase the risk for multiple sclerosis. Brain 2011; 134: 653-64.
7. Confavreux C, Vukusic S. Natural history of multiple sclerosis: a unifying concept. Brain 2006; 129: 606-16.
8. Tallantyre EC, Bo L, Al-Rawashdeh O, et al. Clinico-pathological evidence that axonal loss underlies disability in progressive multiple sclerosis. Mult Scler 2010; 16: 406-11.
9. Leray E, Yaouanq J, Le Page E, et al. Evidence for a two-stage disability progression in multiple sclerosis. Brain 2010; 133: 1900-13.
10. Lassmann H, van Horssen J, Mahad D. Progressive multiple sclerosis: pathology and pathogenesis. Nat Rev Neurol 2012; 8: 647-56.
11. Bermel RA, Rudick RA. Interferon-beta treatment for multiple sclerosis. Neurotherapeutics 2007; 4: 633-46.
12. Johnson KP. Glatiramer acetate for treatment of relapsing-remitting multiple sclerosis. Expert Rev Neurother 2012; 12: 371-84.
13. Kappos L, Polman CH, Freedman MS, et al. Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology 2006; 67: 1242-9.
14. O'Connor P, Filippi M, Arnason B, et al. 250 microg or 500 microg interferon beta-1b versus 20 mg glatiramer acetate in relapsing-remitting multiple sclerosis: a prospective, randomised, multicentre study. Lancet Neurol 2009; 8: 889-97.
15. 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 Key terms Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicentre, randomised, parallel, open-label trial. Lancet Neurol 2008; 7: 903-14.
16. Tedeholm H, Lycke J, Skoog B, et al. Time to secondary progression in patients with multiple sclerosis who were treated with first generation immunomodulating drugs. Mult Scler 2012; 19: 765-74.
17. Shirani A, Zhao Y, Karim ME, et al. Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis. JAMA 2012; 308: 247-56.
18. Kappos L, Freedman MS, Polman CH, et al. Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial. Lancet Neurol 2009; 8: 987-97.
19. Rudick RA, Polman CH. Current approaches to the identification and management of breakthrough disease in patients with multiple sclerosis. Lancet Neurol 2009; 8: 545-59.
20. Hesse D, Krakauer M, Lund H, et al. Breakthrough disease during interferon-[beta] therapy in MS: no signs of impaired biologic response. Neurology 2010; 74: 1455-62.
21. Wong J, Gomes T, Mamdani M, Manno M, O'Connor PW. Adherence to multiple sclerosis disease-modifying therapies in Ontario is low. Can J Neurol Sci 2011; 38: 429-33.
22. Tremlett HL, Oger J. Interrupted therapy: stopping and switching of the beta-interferons prescribed for MS. Neurology 2003; 61: 551-4.
23. Hartung HP, Gonsette R, Konig N, et al. Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet 2002; 360: 2018-25.
24. Yednock TA, Cannon C, Fritz LC, et al. Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 1992; 356: 63-6.
25. Kivisakk P, Healy BC, Viglietta V, et al. Natalizumab treatment is associated with peripheral sequestration of proinflammatory T cells. Neurology 2009; 72: 1922-30.
26. Bornsen L, Christensen JR, Ratzer R, et al. Effect of natalizumab on circulating CD4+ T-cells in multiple sclerosis. PLoS ONE 2012; 7: e47578.
27. Stenner MP, Waschbisch A, Buck D, et al. Effects of natalizumab treatment on Foxp3+ T regulatory cells. PLoS ONE 2008; 3: e3319.
28. Polman CH, O'Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006; 354: 899-910.
29. Rudick RA, Stuart WH, Calabresi PA, et al. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 2006; 354: 911-23.
30. Gunnarsson M, Malmestrom C, Axelsson M, et al. Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab. Ann Neurol 2011; 69: 83-9.
31. Holmen C, Piehl F, Hillert J, et al. A Swedish national post-marketing surveillance study of natalizumab treatment in multiple sclerosis. Mult Scler 2011; 17: 708-19.
32. Tan CS, Koralnik IJ. Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis. Lancet Neurol 2010; 9: 425-37.
33. Gorelik L, Lerner M, Bixler S, et al. Anti-JC virus antibodies: implications for PML risk stratification. Ann Neurol 2010; 68: 295-303.
34. O'Connor PW, Goodman A, Kappos L, et al. Disease activity return during natalizumab treatment interruption in patients with multiple sclerosis. Neurology 2011; 76: 1858-65.
35. West TW, Cree BA. Natalizumab dosage suspension: are we helping or hurting? Ann Neurol 2010; 68: 395-9.
36. Burt RK, Loh Y, Cohen B, et al. Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study. Lancet Neurol 2009; 8: 244-53.
37. Matloubian M, Lo CG, Cinamon G, et al. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 2004; 427: 355-60.
38. Mehling M, Brinkmann V, Antel J, et al. FTY720 therapy exerts differential effects on T cell subsets in multiple sclerosis. Neurology 2008; 71: 1261-7.
39. Vaessen LM, van Besouw NM, Mol WM, Ijzermans JN, Weimar W. FTY720 treatment of kidney transplant patients: a differential effect on B cells, naive T cells, memory T cells and NK cells. Transpl Immunol 2006; 15: 281-8.
40. Mehling M, Lindberg R, Raulf F, et al. Th17 central memory T cells are reduced by FTY720 in patients with multiple sclerosis. Neurology 2010; 75: 403-10.
41. Kappos L, Radue EW, O'Connor P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 2010; 362: 387-401.
42. Cohen JA, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 2010; 362: 402-15.
43. Pelletier D, Hafler DA. Fingolimod for multiple sclerosis. N Engl J Med 2012; 366: 339-47.
44. Jain N, Bhatti MT. Fingolimod-associated macular edema: incidence, detection, and management. Neurology 2012; 78: 672-80.
45. Miller D, Cree B, Dalton C, et al. Study Design and Baseline Characteristics of the INFORMS Study: Fingolimod in Patients with Primary Progressive Multiple Sclerosis. Neurology 2013; 80: P07.116.
46. Singer B, Miller A, Olsson T, et al. Frequency of Infections during Treatment with Teriflunomide: pooled Data from Three Placebo-Controlled Teriflunomide Studies. Neurology 2013; 80: P01.171.
47. O'Connor P, Wolinsky JS, Confavreux C, et al. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med 2011; 365: 1293-303.
48. Wolinsky JS, Narayana PA, Nelson F, et al. Magnetic resonance imaging outcomes from a phase III trial of teriflunomide. Mult Scler 2013; 19: 1310-9.
49. Miller A, Comi G, Confavreux C, et al. Teriflunomide Efficacy and Safety in Patients with Relapsing Multiple Sclerosis: results from TOWER, a Second, Pivotal, Phase 3 Placebo-Controlled Study. Neurology 2013; 80: S01.004.
50. Vermersch P, Czlonkowska A, Grimaldi LM, et al. Teriflunomide versus subcutaneous interferon beta-1a in patients with relapsing multiple sclerosis: a randomised, controlled phase 3 trial. Mult Scler 2014. [Epub ahead of print]. PMID: 24126064
51. Schimrigk S, Brune N, Hellwig K, et al. Oral fumaric acid esters for the treatment of active multiple sclerosis: an open-label, baseline-controlled pilot study. Eur J Neurol 2006; 13: 604-10.
52. 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.
53. Gold R, Kappos L, Arnold DL, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med 2012; 367: 1098-107.
54. Fox RJ, Miller DH, Phillips JT, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med 2012; 367: 1087-97.
55. Scannevin RH, Chollate S, Jung MY, et al. Fumarates promote cytoprotection of central nervous system cells against oxidative stress via the nuclear factor (erythroid-derived 2)-like 2 pathway. J Pharmacol Exp Ther 2012; 341: 274-84.
56. Linker RA, Lee DH, Ryan S, et al. Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain 2011; 134: 678-92.
57. Ellrichmann G, Petrasch-Parwez E, Lee DH, et al. Efficacy of fumaric acid esters in the R6/2 and YAC128 models of Huntington's disease. PLoS ONE 2011; 6: e16172.
58. Noseworthy JH, Wolinsky JS, Lublin FD, et al. Linomide in relapsing and secondary progressive MS: part I: trial design and clinical results. North American Linomide Investigators. Neurology 2000; 54: 1726-33.
59. Polman C, Barkhof F, Sandberg-Wollheim M, et al. Treatment with laquinimod reduces development of active MRI lesions in relapsing MS. Neurology 2005; 64: 987-91.
60. 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.
61. Comi G, Jeffery D, Kappos L, et al. Placebo-controlled trial of oral laquinimod for multiple sclerosis. N Engl J Med 2012; 366: 1000-9.
62. Jolivel V, Luessi F, Masri J, et al. Modulation of dendritic cell properties by laquinimod as a mechanism for modulating multiple sclerosis. Brain 2013; 136: 1048-66.
63. Bruck W, Pfortner R, Pham T, et al. Reduced astrocytic NF-kappaB activation by laquinimod protects from cuprizone-induced demyelination. Acta Neuropathol 2012; 124: 411-24.
64. 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.
65. Hawker K, O'Connor P, Freedman MS, et al. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol 2009; 66: 460-71.
66. Nielsen AS, Miravalle A, Langer-Gould A, et al. Maximally tolerated versus minimally effective dose: the case of rituximab in multiple sclerosis. Mult Scler 2012; 18: 377-8.
67. Kappos L, Li D, Calabresi PA, et al. Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial. Lancet 2011; 378: 1779-87.
68. Franciotta D, Salvetti M, Lolli F, Serafini B, Aloisi F. B cells and multiple sclerosis. Lancet Neurol 2008; 7: 852-8.
69. Piccio L, Naismith RT, Trinkaus K, et al. Changes in B- and T-lymphocyte and chemokine levels with rituximab treatment in multiple sclerosis. Arch Neurol 2010; 67: 707-14.
70. Ireland SJ, Blazek M, Harp CT, et al. Antibody-independent B cell effector functions in relapsing remitting multiple sclerosis: clues to increased inflammatory and reduced regulatory B cell capacity. Autoimmunity 2012; 45: 400-14.
71. Coles AJ, Wing MG, Molyneux P, et al. Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis. Ann Neurol 1999; 46: 296-304.
72. Coles AJ, Compston DA, Selmaj KW, et al. Alemtuzumab versus interferon beta-1a in early multiple sclerosis. N Engl J Med 2008; 359: 1786-180.
73. Coles AJ, Fox E, Vladic A, et al. Alemtuzumab more effective than interferon beta-1a at 5-year follow-up of CAMMS223 clinical trial. Neurology 2012; 78: 1069-78.
74. 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: 1819-28.
75. 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: 1829-39.
76. Bielekova B, Richert N, Howard T, et al. Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon beta. Proc Natl Acad Sci USA 2004; 101: 8705-8.
77. 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.
78. Bielekova B, Catalfamo M, Reichert-Scrivner S, et al. Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis. Proc Natl Acad Sci USA 2006; 103: 5941-6.
79. Gold R, Giovannoni G, Selmaj K, et al. Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial. Lancet 2013; 381: 2167-75.
80. Tortorella C, Bellacosa A, Paolicelli D, et al. Age-related gadolinium-enhancement of MRI brain lesions in multiple sclerosis. J Neurol Sci 2005; 239: 95-9.
81. Khademi M, Dring AM, Gilthorpe JD, et al. Intense inflammation and nerve damage in early multiple sclerosis subsides at older age: a reflection by cerebrospinal fluid biomarkers. PLoS ONE 2013; 8: e63172.
82. Hutchinson M, Kappos L, Calabresi PA, et al. The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL. J Neurol 2009; 256: 405-15.
83. Devonshire V, Havrdova E, Radue EW, et al. Relapse and disability outcomes in patients with multiple sclerosis treated with fingolimod: subgroup analyses of the double-blind, randomised, placebo-controlled FREEDOMS study. Lancet Neurol 2012; 11: 420-8.
84. Axelsson M, Malmestrom C, Gunnarsson M, et al. Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis. Mult Scler 2013; 20: 43-50.
85. Cohen JA, Reingold SC, Polman CH, Wolinsky JS. Disability outcome measures in multiple sclerosis clinical trials: current status and future prospects. Lancet Neurol 2012; 11: 467-76.
86. 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.
87. Khademi M, Kockum I, Andersson ML, et al. Cerebrospinal fluid CXCL13 in multiple sclerosis: a suggestive prognostic marker for the disease course. Mult Scler 2011; 17: 335-43.
88. Lu E, Wang BW, Guimond C, et al. Disease-modifying drugs for multiple sclerosis in pregnancy: a systematic review. Neurology 2012; 79: 1130-5.