Current and future treatments for relapsing-remitting multiple sclerosis

Current Opinion in Drug Discovery and Development

Volumn 13, Issue 2, 2010, Pages 214-225

  Birnbaum, Gary ^a  

^a Minneapolis Clinic of Neurology   (United States)

Author keywords

Disease modifying therapy; Immune modulation; Immune suppressant; MAb; Multiple sclerosis

Indexed keywords

ALEMTUZUMAB; BETA INTERFERON; BETA1A INTERFERON; BG 00012; CLADRIBINE; DACLIZUMAB; EXTAVIA; FINGOLIMOD; FUMARIC ACID DIMETHYL ESTER; GLATIRAMER; INTERFERON BETA SERINE; LAQUINIMOD; METHYLPREDNISOLONE; MITOXANTRONE; NATALIZUMAB; OCRELIZUMAB; RITUXIMAB; TERIFLUNOMIDE; UNCLASSIFIED DRUG;

ADVERSE DRUG REACTION; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALOPECIA; ANAPHYLAXIS; ARTHRALGIA; AUTOIMMUNE HEPATITIS; AUTOIMMUNE HYPERTHYROIDISM; BACKACHE; BLOOD TOXICITY; BONE MARROW SUPPRESSION; BREAST CANCER; CARDIOTOXICITY; CENTRAL NERVOUS SYSTEM LYMPHOMA; CHEST TIGHTNESS; CHILL; CLINICAL TRIAL; DEPRESSION; DIARRHEA; DRUG EFFECT; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; DYSPNEA; ENCEPHALITIS; FATIGUE; FEVER; FLU LIKE SYNDROME; FLUSHING; FOCAL HEMORRHAGIC ENCEPHALITIS; FORCED EXPIRATORY VOLUME; GOODPASTURE SYNDROME; GRAVES DISEASE; HAIRY CELL LEUKEMIA; HEADACHE; HEART PALPITATION; HEART RATE; HEAT SENSATION; HERPES SIMPLEX; HERPES SIMPLEX ENCEPHALITIS; HERPES ZOSTER; HUMAN; HYPERTHYROIDISM; HYPOTHYROIDISM; IDIOPATHIC THROMBOCYTOPENIC PURPURA; IMMUNOMODULATION; IMMUNOSUPPRESSIVE TREATMENT; INFECTION; INFUSION REACTION; JC VIRUS INFECTION; KIDNEY GRAFT REJECTION; LIMB PAIN; LIPOATROPHY; LIVER FAILURE; LIVER TOXICITY; LOW DRUG DOSE; LYMPHOCYTOPENIA; LYMPHOMA; MALIGNANT NEOPLASTIC DISEASE; MELANOMA; MULTIPLE CYCLE TREATMENT; MULTIPLE SCLEROSIS; NAUSEA; NEOPLASM; NEPHROTOXICITY; NONHUMAN; OPPORTUNISTIC INFECTION; PARESTHESIA; POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; PRURITUS; PSORIASIS; RETINA MACULA EDEMA; REVIEW; RHABDOMYOLYSIS; RHINOPHARYNGITIS; RIGOR; RISK BENEFIT ANALYSIS; SHIVERING; SIDE EFFECT; SKIN FIBROSIS; TERATOGENICITY; UPPER ABDOMINAL PAIN; UPPER RESPIRATORY TRACT INFECTION; VIRUS INFECTION;

ANIMALS; HUMANS; IMMUNOLOGIC FACTORS; IMMUNOTHERAPY; MULTIPLE SCLEROSIS, RELAPSING-REMITTING;

EID: 77749270498     PISSN: 13676733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (108)

1. No authors listed: Interferonβ-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. The IFNB Multiple Sclerosis Study Group. Neurology (1993) 43(4):655-661.
2. Paty DW, Li DK: Interferon β-1b is effective in relapsing-remitting 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(4):662-667.
3. Jacobs LD, Cookfair DL, Rudick RA, Herndon RM, Richert JR, Salazar AM, Fischer JS, Goodkin DE, Granger CV, Simon JH, Alam JJ, et al: Intramuscular interferon β-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol (1996) 39(3):285-294.
4. Panitch H, Goodin DS, Francis G, Chang P, Coyle PK, O'Connor P, Monaghan E, Li D, Weinshenker B: Randomized, comparative study of interferon β-1a treatment regimens in MS: The EVIDENCE Trial. Neurology (2002) 59(10):1496-1506.
5. Mikol DD, Barkhof F, Chang P, Coyle PK, Jeffery DR, Schwid SR, Stubinski B, Uitdehaag BM: Comparison of subcutaneous interferon β-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(10):903-914.
6. O'Connor P, Filippi M, Arnason B, Comi G, Cook S, Goodin D, Hartung HP, Jeffery D, Kappos L, Boateng F, Filippov V, et al: 250 μ g or 500 μ g interferon β-1b versus 20 mg glatiramer acetate in relapsing-remitting multiple sclerosis: A prospective, randomised, multicentre study. Lancet Neurol (2009) 8(10): 889-897.
7. Feinstein A: Multiple sclerosis, disease modifying treatments and depression: A critical methodological review. Mult Scler (2000) 6(5):343-348.
8. Durelli L, Ferrero B, Oggero A, Verdun E, Bongioanni MR, Gentile E, Isoardo GL, Ricci A, Rota E, Bergamasco B, Durazzo M, et al: Autoimmune events during interferon β-1b treatment for multiple sclerosis. J Neurol Sci (1999) 162(1):74-83.
9. Yoshida EM, Rasmussen SL, Steinbrecher UP, Erb SR, Scudamore CH, Chung SW, Oger JJ, Hashimoto SA: Fulminant liver failure during interferon β treatment of multiple sclerosis. Neurology (2001) 56(10):1416.
10. Rotondi M, Oliviero A, Profce P, Mone CM, Biondi B, Del Buono A, Mazziotti G, Sinisi AM, Bellastella A, Carella C: Occurrence of thyroid autoimmunity and dysfunction throughout a nine-month follow-up in patients undergoing interferon-β therapy for multiple sclerosis. J Endocrinol Invest (1998) 21(11):748-752.
11. Schwid SR, Goodman AD, Mattson DH: Autoimmune hyperthyroidism in patients with multiple sclerosis treated with interferon β-1b. Arch Neurol (1997) 54(9):1169-1190.
12. van der Voort LF, Visser A, Knol DL, Oudejans CB, Polman CH, Killestein J: Lack of interferon-β bioactivity is associated with the occurrence of relapses in multiple sclerosis. Eur J Neurol (2009) 16(9):1049-1052.
13. Durelli L, Barbero P, Bergui M, Versino E, Bassano MA, Verdun E, Rivoiro C, Ferrero C, Picco E, Ripellino P, Giuliani G, et al: MRI activity and neutralising antibody as predictors of response to interferon β treatment in multiple sclerosis. J Neurol Neurosurg Psychiatry (2008) 79(6):646-651.
14. Hartung HP, Polman C, Bertolotto A, Deisenhammer F, Giovannoni G, Havrdova E, Hemmer B, Hillert J, Kappos L, Kieseier B, Killestein J, et al: Neutralising antibodies to interferon β in multiple sclerosis: Expert panel report. J Neurol (2007) 254(7):827-837.
15. Hemmer B, Stuve O, Kieseier B, Schellekens H, Hartung HP: Immune response to immunotherapy: The role of neutralising antibodies to interferon β in the treatment of multiple sclerosis. Lancet Neurol (2005) 4(7):403-412.
16. Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, Myers LW, Panitch HS, Rose JW, Schiffer RB: 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(7):1268-1276.
17. Ge Y, Grossman RI, Udupa JK, Fulton J, Constantinescu CS, Gonzales-Scarano F, Babb JS, Mannon LJ, Kolson DL, Cohen JA: Glatiramer acetate (Copaxone) treatment in relapsing-remitting MS: Quantitative MR assessment. Neurology (2000) 54(4):813-817.
18. Filippi M, Rovaris M, Rocca MA, Sormani MP, Wolinsky JS, Comi G: Glatiramer acetate reduces the proportion of new MS lesions evolving into 'black holes'. Neurology (2001) 57(4):731-733.
19. Comi G, Filippi M, Wolinsky JS: European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging-Measured disease activity and burden in patients with relapsing multiple sclerosis. European/Canadian Glatiramer Acetate Study Group. Ann Neurol (2001) 49(3):290-297.
20. Miller A, Spada V, Beerkircher D, Kreitman RR: Long-term (up to 22 years), open-label, compassionate-use study of glatiramer acetate in relapsing-remitting multiple sclerosis. Mult Scler (2008) 14(4):494-499.
21. Ford CC, Johnson KP, Lisak RP, Panitch HS, Shifronis G, Wolinsky JS: A prospective open-label study of glatiramer acetate: Over a decade of continuous use in multiple sclerosis patients. Mult Scler (2006) 12(3):309-320.
22. Schrempf W, Ziemssen T: Glatiramer acetate: Mechanisms of action in multiple sclerosis. Autoimmun Rev (2007) 6(7):469-475.
23. Zwibel HL: Glatiramer acetate in treatment-naïve and prior interferon-p-1b-treated multiple sclerosis patients. Acta Neurol Scand (2006) 113(6):378-386.
24. Brenner T, Arnon R, Sela M, Abramsky O, Meiner Z, Riven-Kreitman R, Tarcik N, Teitelbaum D: Humoral and cellular immune responses to copolymer 1 in multiple sclerosis patients treated with Copaxone. J Neuroimmunol (2001) 115(1-2):152-160.
25. Neumann H, Csepregi A, Sailer M, Malfertheiner P: Glatiramer acetate induced acute exacerbation of autoimmune hepatitis in a patient with multiple sclerosis. J Neurol (2007) 254(6): 816-817.
26. Frohman EM, Brannon K, Alexander S, Sims D, Phillips JT, O'Leary S, Hawker K, Racke MK: Disease modifying agent related skin reactions in multiple sclerosis: Prevention, assessment, and management. Mult Scler (2004) 10(3):302-307.
27. Eshghi S, Vogelezang MG, Hynes RO, Griffth LG, Lodish HF: a4p1 integrin and erythropoietin mediate temporally distinct steps in erythropoiesis: Integrins in red cell development. J Cell Biol (2007) 177(5):871-880.
28. Yan HH, Cheng CY: Laminin <3 forms a complex with p3 and 3 chains that serves as the ligand for a 6| 1-integrin at the apical ectoplasmic specialization in adult rat testes. J Biol Chem. 2006;281;25:17286-17303.
29. Bauer M, Brakebusch C, Coisne C, Sixt M, Wekerle H, Engelhardt B, Fassler R: p1 integrins differentially control extravasation of infammatory cell subsets into the CNS during autoimmunity. Proc Natl Acad Sci USA (2009) 106(6):1920-1925.
30. Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, et al: A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med (2006) 354(9):899-910.
31. Rudick RA, Stuart WH, Calabresi PA, Confavreux C, Galetta SL, Radue EW, Lublin FD, Weinstock-Guttman B, Wynn DR, Lynn F, Panzara MA, et al: Natalizumab plus interferon β-1a for relapsing multiple sclerosis. N Engl J Med (2006) 354(9):911-923. (Pubitemid 43313658)
32. Calabresi PA, Giovannoni G, Confavreux C, Galetta SL, Havrdova E, Hutchinson M, Kappos L, Miller DH, O'Connor PW, Phillips JT, Polman CH, et al: The incidence and signifcance of anti-natalizumab antibodies: Results from AFFIRM and SENTINEL. Neurology (2007) 69(14):1391-1403.
33. No authors listed: Natalizumab (Tysabri) for relapsing multiple sclerosis. Med Lett Drugs Ther (2005) 47(1202):13-15.
34. Oturai AB, Koch-Henriksen N, Petersen T, Jensen PE, Sellebjerg F, Sorensen PS: Effcacy of natalizumab in multiple sclerosis patients with high disease activity: A Danish nationwide study. Eur J Neurol (2009) 16(3):420-423.
35. Khalili K, White MK, Lublin F, Ferrante P, Berger JR: Reactivation of JC virus and development of PML in patients with multiple sclerosis. Neurology (2007) 68(13):985-990.
36. Kleinschmidt-DeMasters BK, Tyler KL: Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon β-1a for multiple sclerosis. N Engl J Med (2005) 353(4):369-374.
37. Langer-Gould A, Atlas SW, Green AJ, Bollen AW, Pelletier D: Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med (2005) 353(4):375-381.
38. UPDATE 1-EU agency reports 24th case of Tysabri infection. Reuters, London, UK (2009). www.reuters.com/article/ rbssHealthcareNews/ idUSLT39797520091029.
39. Elan, Biogen change Tysabri label due to PML risk. Reuters, Dublin, Ireland (2009). www.reuters.com/article/rbssHealthcareNews/ idUSL718499120091107
40. Linda H, von Heijne A, Major EO, Ryschkewitsch C, Berg J, Olsson T, Martin C: Progressive multifocal leukoencephalopathy after natalizumab monotherapy. N Engl J Med (2009) 361(11): 1081-1087.
41. Wenning W, Haghikia A, Laubenberger J, Clifford DB, Behrens PF, Chan A, Gold R: Treatment of progressive multifocal leukoencephalopathy associated with natalizumab. N Engl J Med (2009) 361(11):1075-1080.
42. Comi G: Treatment of multiple sclerosis: Role of natalizumab. Neurol Sci (2009) 30(Suppl 2):S155-S158.
43. Ismail A, Kemp J, Sharrack B: Melanoma complicating treatment with natalizumab (tysabri) for multiple sclerosis. J Neurol (2009) 256(10):1771-1772.
44. Mullen JT, Vartanian TK, Atkins MB: Melanoma complicating treatment with natalizumab for multiple sclerosis. N Engl J Med (2008) 358(6):647-648.
45. Schweikert A, Kremer M, Ringel F, Liebig T, Duyster J, Stuve O, Hemmer B, Berthele A: Primary central nervous system lymphoma in a patient treated with natalizumab. Ann Neurol (2009) 66(3): 403-406.
46. Hartung HP, Gonsette R, Konig N, Kwiecinski H, Guseo A, Morrissey SP, Krapf H, Zwingers T: Mitoxantrone in progressive multiple sclerosis: A placebo-controlled, double-blind, randomised, multicentre trial. Lancet (2002) 360(9350):2018-2025.
47. Buttinelli C, Clemenzi A, Borriello G, Denaro F, Pozzilli C, Fieschi C: Mitoxantrone treatment in multiple sclerosis: A 5-year clinical and MRI follow-up. Eur J Neurol (2007) 14(11):1281-1287.
48. Goffette S, van Pesch V, Vanoverschelde JL, Morandini E, Sindic CJ: Severe delayed heart failure in three multiple sclerosis patients previously treated with mitoxantrone. J Neurol (2005) 252(10):1217-1222.
49. Pascual AM, Tellez N, Bosca I, Mallada J, Belenguer A, Abellan I, Sempere AP, Fernandez P, Magraner MJ, Coret F, Sanz MA, et al: Revision of the risk of secondary leukemia after mitoxantrone in multiple sclerosis populations is required. Mult Scler (2009) 15(11):1303-1310.
50. Goodin DS, Arnason BG, Coyle PK, Frohman EM, Paty DW: The use of mitoxantrone (Novantrone) for the treatment of multiple sclerosis: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology (2003) 61(10):1332-1338.
51. Beutler E, Koziol JA, McMillan R, Sipe JC, Romine JS, Carrera CJ: Marrow suppression produced by repeated doses of cladribine. Acta Haematol (1994) 91(1):10-15.
52. Sipe JC, Romine JS, Koziol JA, McMillan R, Zyroff J, Beutler E: Cladribine in treatment of chronic progressive multiple sclerosis. Lancet (1994) 344(8914):9-13.
53. Dighiero G: Adverse and benefcial immunological effects of purine nucleoside analogues. Hematol Cell Ther (1996) 38(Suppl 2):S75-S81.
54. Rice GP, Filippi M, Comi G: Cladribine and progressive MS: clinical and MRI outcomes of a multicenter controlled trial. Cladribine MRI Study Group. Neurology (2000) 54(5):1145-1155.
55. Giovannoni G, Comi G, Cook S, Rammohan K, Rieckmann P, Sørensen PS, Vermersch P, Chang P, Hamlett A, Musch B, Greenberg SJ, et al: A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N Engl J Med (2010) 362(5):416-426.
56. Comi G, Cook S, Giovannoni G, Rammohan K, Rieckmann P, Sørensen PS, Vermersch P, Chang P, Hamlett A, Musch B, Fevr T, et al: Reductions in MRI activity in relapsing-remitting multiple sclerosis achieved with cladribine tablets in the 96-week, phase III, double-blind, placebo-controlled CLARITY study. 25th Congress of the European Committee for the Treatment and Research in Multiple Sclerosis Düsseldorf, Germany (2009).
57. Sørensen PS, Comi G, Cook S, Giovannoni G, Rammohan K, Rieckmann P, Vermersch P, Chang P, Hamlett A, Viglietta V, Verjee R, et al: Effects of cladribine tablets on haematological profles in patients with relapsing-remitting multiple sclerosis in the 96-week, phase III, double-blind, placebo-controlled CLARITY study. 25th Congress of the European Committee for Treatment and Research in Multiple Sclerosis, Düsseldorf, Germany (2009).
58. Leleu X, Soumerai J, Roccaro A, Hatjiharissi E, Hunter ZR, Manning R, Ciccarelli BT, Sacco A, Ioakimidis L, Adamia S, Moreau AS, et al: Increased incidence of transformation and myelodysplasia/acute leukemia in patients with Waldenstrom macroglobulinemia treated with nucleoside analogs. J Clin Oncol (2009) 27(2):250-255.
59. Luo ZJ, Tanaka T, Kimura F, Miyasaka M: Analysis of the mode of action of a novel immunosuppressant FTY720 in mice. Immunopharmacology (1999) 41(3):199-207.
60. Brinkmann V, Davis MD, Heise CE, Albert R, Cottens S, Hof R, Bruns C, Prieschl E, Baumruker T, Hiestand P, Foster CA, et al: The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J Biol Chem (2002) 277(24):21453-21457.
61. Mandala S, Hajdu R, Bergstrom J, Quackenbush E, Xie J, Milligan J, Thornton R, Shei GJ, Card D, Keohane C, Rosenbach M, et al: Alteration of lymphocyte traffcking by sphingosine-1-phosphate receptor agonists. Science (2002) 296(5566):346-349.
62. Xie JH, Nomura N, Koprak SL, Quackenbush EJ, Forrest MJ, Rosen H: Sphingosine-1-phosphate receptor agonism impairs the effciency of the local immune response by altering traffcking of naïve and antigen-activated CD4+ T cells. J Immunol (2003) 170(7):3662-3670.
63. Jaillard C, Harrison S, Stankoff B, Aigrot MS, Calver AR, Duddy G, Walsh FS, Pangalos MN, Arimura N, Kaibuchi K, Zalc B, et al: Edg8/ S1P5: An oligodendroglial receptor with dual function on process retraction and cell survival. J Neurosci (2005) 25(6): 1459-1469.
64. Kappos L, Antel J, Comi G, Montalban X, O'Connor P, Polman CH, Haas T, Korn AA, Karlsson G, Radue EW: Oral fngolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med (2006) 355(11): 1124-1140.
65. Budde K, Schutz M, Glander P, Peters H, Waiser J, Liefeldt L, Neumayer HH, Bohler T: FTY720 (fngolimod) in renal transplantation. Clin Transplant (2006) 20(Suppl 17):17-24.
66. Papadopoulos D, Rundle J, Patel R, Marshall I, Stretton J, Eaton R, Richardson JC, Gonzalez MI, Philpott KL, Reynolds R: FTY720 ameliorates MOG-induced experimental autoimmune encephalomyelitis by suppressing both cellular and humoral immune responses. J Neurosci Res (2009) 88(2):346-359.
67. Webb M, Tham CS, Lin FF, Lariosa-Willingham K, Yu N, Hale J, Mandala S, Chun J, Rao TS: Sphingosine 1-phosphate receptor agonists attenuate relapsing-remitting experimental autoimmune encephalitis in SJL mice. J Neuroimmunol (2004) 153(1-2):108-121.
68. Fujino M, Funeshima N, Kitazawa Y, Kimura H, Amemiya H, Suzuki S, Li XK: Amelioration of experimental autoimmune encephalomyelitis in Lewis rats by FTY720 treatment. J Pharmacol Exp Ther (2003) 305(1):70-77.
69. Kappos L, Gold R, Miller DH, Macmanus DG, Havrdova E, Limmroth V, Polman CH, Schmierer K, Yousry TA, Yang M, Eraksoy M, et al: Effcacy 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(9648):1463-1472.
70. Cohen J, Pelletier J, Kappos L, Montalban X, Hartung H-P, Comi G, Khatri BO, Barkhof F, Stites T, Jin J, Wu S, et al: Oral fngolimod (FTY720) versus interferon β-1a in relapsing-remitting multiple sclerosis: Results from a phase III study (TRANSFORMS). Annual Meeting of the American Academy of Neurology, Seattle, WA, USA (2009) 61:Abs S21.004.
71. Leypoldt F, Munchau A, Moeller F, Bester M, Gerloff C, Heesen C: Hemorrhaging focal encephalitis under fngolimod (FTY720) treatment: A case report. Neurology (2009) 72(11):1022-1024.
72. Novartis AG: Two-year phase III study shows Novartis oral MS therapy FTY720 signifcantly reduces relapses and disability progression. Press Release (2009): September 30.
73. Wiendl H, Hohlfeld R: Therapeutic approaches in multiple sclerosis: Lessons from failed and interrupted treatment trials. BioDrugs (2002) 16(3):183-200.
74. Yang JS, Xu LY, Xiao BG, Hedlund G, Link H: Laquinimod (ABR-215062) suppresses the development of experimental autoimmune encephalomyelitis, modulates the Th1/Th2 balance and induces the Th3 cytokine TGF-β in Lewis rats. J Neuroimmunol (2004) 156(1-2):3-9.
75. Birnberg T, Jung S: Effect of Laquinimod on the Dendritic Cell Compartment. Annual Meeting of the American Academy of Neurology, Seattle, WA, USA (2009) 61:Abs P01.113.
76. Or-Bach R, Sonis P, Gurevich M, Achiron A: Down regulation of antigen presentation and infammatory pathways by laquinimod in cultured peripheral blood mononuclear cells of untreated multiple sclerosis patients and healthy subjects. Annual Meeting of the American Academy of Neurology, Seattle, WA, USA (2009) 61:Abs P01.120.
77. Hayardeny L, Feigelson S, Grabovsky V, Kaye J, Keshet R, Cinamon G, Alon R: The effect of laquinimod on lymphocyte VLA-4 properties under shear fow conditions. Annual Meeting of the American Academy of Neurology, Seattle, WA, USA (2009) 61:Abs S47.008.
78. Comi G, Pulizzi A, Rovaris M, Abramsky O, Arbizu T, Boiko A, Gold R, Havrdova E, Komoly S, Selmaj K, Sharrack B, 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(9630):2085-2092.
79. O'Connor PW, Li D, Freedman MS, Bar-Or A, Rice GP, Confavreux C, Paty DW, Stewart JA, Scheyer R: A phase II study of the safety and effcacy of terifunomide in multiple sclerosis with relapses. Neurology (2006) 66(6):894-900.
80. Miljkovic D, Samardzic T, Mostarica Stojkovic M, Stosic-Grujicic S, Popadic D, Trajkovic V: Lefunomide inhibits activation of inducible nitric oxide synthase in rat astrocytes. Brain Res (2001) 889(1-2):331-338 (Pubitemid 32146304)
81. Arava & pregnancy: Counseling guidelines for women of childbearing potential: sanof-aventis, Bridgewater, NJ, USA (2008). www.arava.com/hcp/about/ pregnancy.aspx
82. Rostami Yazdi M, Mrowietz U: Fumaric acid esters. Clin Dermatol (2008) 26(5):522-526.
83. Schilling S, Goelz S, Linker R, Luehder F, Gold R: Fumaric acid esters are effective in chronic experimental autoimmune encephalomyelitis and suppress macrophage infltration. Clin Exp Immunol (2006) 145(1):101-107.
84. Hoefnagel JJ, Thio HB, Willemze R, Bouwes Bavinck JN: Long-term safety aspects of systemic therapy with fumaric acid esters in severe psoriasis. Br J Dermatol (2003) 149(2):363-369.
85. Coles AJ, Cox A, Le Page E, Jones J, Trip SA, Deans J, Seaman S, Miller DH, Hale G, Waldmann H, Compston DA: The window of therapeutic opportunity in multiple sclerosis: Evidence from monoclonal antibody therapy. J Neurol (2006) 253(1): 98-108.
86. Coles AJ, Wing MG, Molyneux P, Paolillo A, Davie CM, Hale G, Miller D, Waldmann H, Compston A: Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis. Ann Neurol (1999) 46(3):296-304.
87. Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, Norris K, Tandon PK: Alemtuzumab vs interferon β-1a in early multiple sclerosis. N Engl J Med (2008) 359(17):1786-1801.
88. Moreau T, Coles A, Wing M, Isaacs J, Hale G, Waldmann H, Compston A: Transient increase in symptoms associated with cytokine release in patients with multiple sclerosis. Brain (1996) 119(Pt 1):225-237.
89. Clatworthy MR, Wallin EF, Jayne DR: Anti-glomerular basement membrane disease after alemtuzumab. N Engl J Med (2008) 359(7):768-769.
90. Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, Bar-Or A, Panzara M, Sarkar N, Agarwal S, Langer-Gould A, et al: B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med (2008) 358(7):676-688.
91. Cross AH, Stark JL, Lauber J, Ramsbottom MJ, Lyons JA: Rituximab reduces B cells and T cells in cerebrospinal fuid of multiple sclerosis patients. J Neuroimmunol (2006) 180(1-2):63-70.
92. Bayry J, Lacroix-Desmazes S, Kazatchkine MD, Kaveri SV: Monoclonal antibody and intravenous immunoglobulin therapy for rheumatic diseases: Rationale and mechanisms of action. Nat Clin Pract Rheumatol (2007) 3(5):262-272.
93. Maloney DG, Grillo-Lopez AJ, White CA, Bodkin D, Schilder RJ, Neidhart JA, Janakiraman N, Foon KA, Liles TM, Dallaire BK, Wey K, et al: IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood (1997) 90(6):2188-2195.
94. Thomas DA, O'Brien S, Bueso-Ramos C, Faderl S, Keating MJ, Giles FJ, Cortes J, Kantarjian HM: Rituximab in relapsed or refractory hairy cell leukemia. Blood (2003) 102(12):3906-3911.
95. Pender MP: Preventing and curing multiple sclerosis by controlling Epstein-Barr virus infection. Autoimmun Rev (2009) 8(7):563-568.
96. Ascherio A, Munger KL: Environmental risk factors for multiple sclerosis. Part I: The role of infection. Ann Neurol (2007) 61(4):288-299. (Pubitemid 46676728)
97. Nielsen TR, Pedersen M, Rostgaard K, Frisch M, Hjalgrim H: Correlations between Epstein-Barr virus antibody levels and risk factors for multiple sclerosis in healthy individuals. Mult Scler (2007) 13(3):420-423.
98. Waubant E: Spotlight on anti-CD20. Int MS J (2008) 15(1):19-25.
99. Hawker K, O'Connor P, Freedman MS, Calabresi PA, Antel J, Simon J, Hauser S, Waubant E, Vollmer T, Panitch H, Zhang J, et al: Rituximab in patients with primary progressive multiple sclerosis: Results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol (2009) 66(4):460-471.
100. Molloy ES, Calabrese LH: Progressive multifocal leukoencephalopathy in patients with rheumatic diseases: Are patients with systemic lupus erythematosus at particular risk? Autoimmun Rev (2008) 8(2):144-146.
101. Calabrese LH, Molloy ES: Progressive multifocal leucoencephalopathy in the rheumatic diseases: Assessing the risks of biological immunosuppressive therapies. Ann Rheum Dis (2008) 67(Suppl 3):iii64-iii65.
102. Roche AG: Roche reports positive phase II results with ocrelizumab in relapsing-remitting multiple sclerosis (RRMS). Press Release (2009): December 04.
103. Vincenti F, Kirkman R, Light S, Bumgardner G, Pescovitz M, Halloran P, Neylan J, Wilkinson A, Ekberg H, Gaston R, Backman L, et al: Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group. N Engl J Med (1998) 338(3):161-165.
104. Bielekova B, Richert N, Howard T, Blevins G, Markovic-Plese S, McCartin J, Frank JA, Wurfel J, Ohayon J, Waldmann TA, McFarland HF, et al: Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon β. Proc Natl Acad Sci USA (2004) 101(23): 8705-8708.
105. Rose JW, Burns JB, Bjorklund J, Klein J, Watt HE, Carlson NG: Daclizumab phase II trial in relapsing and remitting multiple sclerosis: MRI and clinical results. Neurology (2007) 69(8):785-789.
106. Rose JW, Watt HE, White AT, Carlson NG: Treatment of multiple sclerosis with an anti-interleukin-2 receptor monoclonal antibody. Ann Neurol (2004) 56(6):864-867.
107. Bielekova B, Howard T, Packer AN, Richert N, Blevins G, Ohayon J, Waldmann TA, McFarland HF, Martin R: Effect of anti-CD25 antibody daclizumab in the inhibition of infammation and stabilization of disease progression in multiple sclerosis. Arch Neurol (2009) 66(4):483-489.
108. Montalban X, Wynn D, Kaufman M, Wang M, Fong A: Preliminary CHOICE results: A phase 2, randomised, double-blind, placebo-controlled multicentre study of subcutaneous daclizumab in patients with active, relapsing forms of multiple sclerosis on interferon beta. 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis & 12th Annual Conference of Rehabilitation in MS, Prague, Czech Republic (2007).