Therapy of MS

Clinical Neurology and Neurosurgery

Volumn 112, Issue 5, 2010, Pages 365-385

  Vosoughi, Reza ^a   Freedman, Mark S ^a  

^a UNIVERSITY OF OTTAWA   (Canada)

Author keywords

Disease modifying; Emerging therapies; Multiple sclerosis; Relapsing remitting multiple sclerosis; Therapy; Treatment

Indexed keywords

ALEMTUZUMAB; BETA INTERFERON; BETA1A INTERFERON; BG 00012; CAMPTH 1H; CLADRIBINE; CORTICOSTEROID; CYCLOPHOSPHAMIDE; DACLIZUMAB; DRUG ANTIBODY; FINGOLIMOD; FUMARIC ACID DIMETHYL ESTER; GAMMA INTERFERON; GILENIA; GLATIRAMER; GLUCOCORTICOID; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IMMUNOMODULATING AGENT; INTERFERON; INTERFERON BETA SERINE; LAQUINIMOD; LIVER ENZYME; METHYLPREDNISOLONE; MINOCYCLINE; MITOXANTRONE; MONOCLONAL ANTIBODY; NATALIZUMAB; NEUTRALIZING ANTIBODY; PLACEBO; RITUXIMAB; ROQUINIMEX; TERIFLUNOMIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ADD ON THERAPY; ALLERGIC ENCEPHALOMYELITIS; ALOPECIA; AMENORRHEA; ANXIETY; ARTHRALGIA; ASTHENIA; ATRIOVENTRICULAR BLOCK; AUTOIMMUNE DISEASE; BRADYCARDIA; BUDD CHIARI SYNDROME; BURKITT LYMPHOMA; CARDIOTOXICITY; CHEST TIGHTNESS; CHILL; CLINICAL TRIAL; DEMYELINATION; DEPRESSION; DIARRHEA; DRUG DOSAGE FORM COMPARISON; DRUG DOSE COMPARISON; DRUG EFFECT; DRUG EFFICACY; DRUG ERUPTION; DRUG FATALITY; DRUG FEVER; DRUG HYPERSENSITIVITY; DRUG INDUCED HEADACHE; DRUG MECHANISM; DRUG MEGADOSE; DRUG SAFETY; DRUG WITHDRAWAL; DYSPNEA; EARLY INTERVENTION; FATIGUE; FLU LIKE SYNDROME; FLUSHING; GASTROENTERITIS; GONAD DYSFUNCTION; GRAVES DISEASE; HAIRY CELL LEUKEMIA; HEART INFARCTION; HEART PALPITATION; HEMATOLOGIC DISEASE; HUMAN; HYPERTENSION; IDIOPATHIC THROMBOCYTOPENIC PURPURA; IMMUNOMODULATION; INFECTION; INJECTION SITE NECROSIS; INJECTION SITE REACTION; LEUKOPENIA; LIMB PAIN; LIVER FUNCTION TEST; LIVER NECROSIS; LIVER TOXICITY; LOW DRUG DOSE; LOWER RESPIRATORY TRACT INFECTION; LYMPHOCYTOPENIA; MALAISE; MALIGNANT NEOPLASTIC DISEASE; MENTAL DISEASE; MESENCHYMAL STEM CELL TRANSPLANTATION; MULTIPLE SCLEROSIS; MUSCLE HYPERTONIA; MYALGIA; MYASTHENIA; NAUSEA; NAUSEA AND VOMITING; NEPHROTOXICITY; NEUROTOXICITY; NONHODGKIN LYMPHOMA; NONHUMAN; OPPORTUNISTIC INFECTION; PAIN; PANCREATITIS; PANCYTOPENIA; PARESTHESIA; PERICARDITIS; PLEURA EFFUSION; PRURITUS; RETINA MACULA EDEMA; REVIEW; RHEUMATOID ARTHRITIS; RHINOPHARYNGITIS; RIGOR; SIDE EFFECT; SINGLE DRUG DOSE; SKIN TOXICITY; SUICIDAL IDEATION; SUICIDE ATTEMPT; TACHYCARDIA; TERATOGENICITY; TREATMENT DURATION; TREATMENT RESPONSE; URINARY TRACT INFECTION; URTICARIA; VAGINITIS; VOMITING;

DRUG THERAPY; HUMANS; IMMUNOLOGIC FACTORS; INTERFERON-BETA; MULTIPLE SCLEROSIS; STEM CELL TRANSPLANTATION;

EID: 77951915259     PISSN: 03038467     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.clineuro.2010.03.010     Document Type: Review

References (328)

1. Lublin F.D., and Reingold S.C. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 46 4 (1996) 907-911
2. Pantich H.S., Hirsch R.L., Schindler J., and Johnson K.P. Treatment of multiple sclerosis with gamma-interferons: exacerbations associated with activation on immune system. Neurology 37 7 (1987) 1097-1102
3. Pantich H.S., Hirsch R.L., Haley A.S., and Johnson K.P. Exacerbations of multiple sclerosis in patients treated with gamma-interferon. Lancet 1 8538 (1987) 893-895
4. Knobler R.L., Panitch H.S., Braheny S.L., Sipe J.C., Rice G.P., Huddlestone J.R., et al. Systemic alpha-interferon therapy of multiple sclerosis. Neurology 34 10 (1984) 1273-1279
5. Panitch H.S. Systemic alpha-interferon in multiple sclerosis. Long-term patient follow-up. Arch Neurol 44 1 (1987) 61-63
6. Camenga D.L., Johnson K.P., Alter M., Engelhardt C.D., Fishman P.S., Greenstein J.I., et al. Systemic recombinant alpha-2 interferon therapy in relapsing multiple sclerosis. Arch Neurol 43 12 (1986) 1239-1246
7. Durelli L., Bongioanni M.R., Cavallo R., Ferrero B., Ferri R., Ferrio M.F., et al. Chronic systemic high-dose recombinant interferon alfa-2a reduces exacerbation rate. MRI signs of disease activity, and lymphocyte interferon gamma production in relapsing-remitting multiple sclerosis. Neurology 44 3 Pt 1 (1994) 406-413
8. Durelli L., Bongioanni M.R., Ferrero B., Ferri R., Imperiale D., Bradac G.B., et al. Interferon alpha-2a treatment of relapsing-remitting multiple sclerosis: disease activity resumes after stopping treatment. Neurology 47 1 (1996) 123-129
9. Myhr K.M., Riise T., Green Lilleås F.E., Beiske T.G., Celius E.G., Edland A., et al. Interferon-alpha2a reduces MRI disease activity in relapsing-remitting multiple sclerosis. Norwegian Study Group on Interferon-alpha in Multiple Sclerosis. Neurology 52 5 (1999) 1049-1056
10. Brod S.A., Lindsey J.W., Vriesendorp F.S., Ahn C., Henninger E., Narayana P.A., et al. Ingested IFN-alpha: results of a pilot study in relapsing-remitting MS. Neurology 57 5 (2001) 845-852
11. The IFNB Multiple Sclerosis Study Group. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 43 4 (1993) 655-661
12. Paty D.W., and Li D.K. Interferon beta-lb is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 43 4 (1993) 662-667
13. The IFNB Multiple Sclerosis Study Group, the University of British Columbia MS/MRI Analysis Group. Interferon beta-1b in the treatment of multiple sclerosis. Final outcome of the randomized controlled trial. Neurology 45 7 (1995) 1277-1285
14. Jacobs L.D., Cookfair D.L., Rudick R.A., Herndon R.M., Richert J.R., Salazar A.M., et al. Intramuscular interferon beta-1a for disease progression in exacerbating remitting multiple sclerosis. Ann Neurol 39 3 (1996) 285-294
15. PRISMS (Prevention of Relapses Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. Lancet 352 9139 (1998) 1498-1504
16. Li D.K., and Paty D.W. 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 46 2 (1999) 197-206
17. Durelli L., Verdun E., Barbero P., Bergui M., Versino E., Ghezzi A., 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 359 9316 (2002) 1453-1460
18. Panitch H., Goodin D.S., Francis G., Chang P., Coyle P.K., O'Connor P., et al. Randomized, comparative study of interferon beta-1a treatment regimens in MS: the EVIDENCE Trial. Neurology 59 10 (2002) 1496-1506
19. Arnason B.G. Interferon beta in multiple sclerosis. Clin Immunol Immunopathol 81 1 (1996) 1-11
20. Huang Y.M., Stoyanova N., Jin Y.P., Teleshova N., Hussien Y., Xiao B.G., et al. Altered phenotype and function of blood dendritic cells in multiple sclerosis are modulated by IFN-beta and IL-10. Clin Exp Immunol 124 2 (2001) 306-314
21. Shapiro S., Galboiz Y., Lahat N., Kinarty A., and Miller A. The 'immunological-synapse' at its APC side in relapsing and secondary-progressive multiple sclerosis: modulation by interferon-beta. J Nuroimmunol 144 1/2 (2003) 116-124
22. Zang Y., Hong J., Robinson R., Li S., Rivera V.M., and Zhang J.Z. Immune regulatory properties and interactions of Copolymer-I and beta-interferon 1a in multiple sclerosis. J Neuroimmunol 137 1/2 (2003) 144-153
23. Ozenci V., Kouwenhoven M., Teleshova N., Pashenkov M., Fredrikson S., and Link H. Multiple sclerosis: pro- and anti-inflammatory cytokines and metalloproteinases are affected differentially by treatment with IFN-beta. J Neuroimmunol 108 1/2 (2000) 236-243
24. Ozenci V., Kouwenhoven M., Huang Y.M., Kivisäkk P., and Link H. Multiple sclerosis is associated with an imbalance between tumour necrosis factor-alpha (TNF-alpha)- and IL-10-secreting blood cells that is corrected by interferon-beta (IFN-beta) treatment. Clin Exp Immunol 120 1 (2000) 147-153
25. Prat A., Al-Asmi A., Duquette P., and Antel J.P. Lymphocyte migration and multiple sclerosis: relation with disease course and therapy. Ann Neurol 46 2 (1999) 253-256
26. Yushchenko M., Mäder M., Elitok E., Bitsch A., Dressel A., Tumani H., et al. Interferon-beta-1 b decreased matrix metalloproteinase-9 serum levels in primary progressive multiple sclerosis. J Neurol 250 10 (2003) 1224-1228
27. European Study Group on Interferon beta-1b in secondary progressive MS. Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive MS. Lancet 352 9139 (1998) 1491-1497
28. Mark D.F., Lu S.D., Creasey A.A., Yamamoto R., and Lin L.S. Site-specific mutagenesis of the human fibroblast interferon gene. Proc Natl Acad Sci USA 81 18 (1984) 5662-5666
29. Ebers G., Traboulsee A., Langdon D., Goodin D., Konieczny A., and for the Betaseron/Betaferon LTF Study Group. The interferon beta-1b 16-year long-term follow-up study: the results. Presented at the 58th annual meeting of the American Academy of Neurology. San Diego, CA (2006) PO1.079
30. Trojano M., Pellegrini F., Fuiani A., Paolicelli D., Zipoli V., Zimatore G.B., et al. New natural history of interferon beta-treated relapsing multiple sclerosis. Ann Neurol 61 4 (2007) 300-306
31. Chernajovsky Y., Mory Y., Chen L., Marks Z., Novick D., Rubinstein M., et al. Efficient constitutive production of human fibroblast interferon by hamster cells transformed with the IFN-beta 1 gene fused to an SV40 early promoter. DNA 3 4 (1984) 297-308
32. The Once Weekly Interferon for MS Study Group. Evidence of interferon beta-1a dose response in relapsing-remitting MS: the OWIMS Study. Neurology 53 4 (1999) 679-686
33. Freedman M.S., Francis G.S., Sanders E.A., Rice G.P., O'Connor P., Comi G., et al. Randomized study of once-weekly interferon beta-1a therapy in relapsing multiple sclerosis: three-year data from the OWIMS study. Mult Scler 11 1 (2005) 41-45
34. Oger J., Francis G., Chang P., and PRISMS study group. Prospective assessment of changing from placebo to IFN beta-1a in relapsing MS: the PRISMS study. J Neurol Sci 237 1/2 (2005) 45-52
35. PRISMS Study Group, University of British Columbia MS/MRI Analysis Group. PRISMS-4: long-term efficacy of interferon-beta-1a in relapsing MS. Neurology 56 12 (2001) 1628-1636
36. Rudick R.A., Goodkin D.E., Jacobs L.D., Cookfair D.L., Herndon R.M., Richert J.R., et al. Impact of interferon beta-1a on neurologic disability in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Neurology 49 2 (1997) 358-363
37. Simon J.H., Jacobs L.D., Campion M., Wende K., Simonian N., Cookfair D.L., et al. Magnetic resonance studies of intramuscular interferon beta-1a for relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group. Ann Neurol 43 1 (1998) 79-87
38. Teitelbaum D., Fridkis-Hareli M., Arnon R., and Sela M. Copolymer 1 inhibits chronic relapsing experimental allergic encephalomyelitis induced by proteolipid protein (PLP) peptides in mice and interferes with PLPspecific T cell responses. J Neuroimmunol 64 2 (1996) 209-217
39. Teitelbaum D., Meshorer A., Hirshfield T., Arnon R., and Sela M. Suppression of experimental allergic encephalomyelitis by a synthetic polypeptide. Eur J Immunol 1 4 (1971) 242-248
40. Fridkis-Hareli M., Teitelbaum D., Pecht I., Arnon R., and Sela M. Binding of copolymer 1 and myelin basic protein leads to clustering of class II MHC molecules on antigen-presenting cells. Int Immunol 9 7 (1997) 925-934
41. Aharoni R., Schlegel P.G., Teitelbaum D., Roikhel-Karpov O., Chen Y., Arnon R., et al. Studies on the mechanism and specificity of the effect of the synthetic random copolymer GLAT on graft-versus-host disease. Immunol Lett 58 2 (1997) 79-87
42. Miller A., Shapiro S., Gershtein R., Kinarty A., Rawashdeh H., Honigman S., et al. Treatment of multiple sclerosis with copolymer-1 (Copaxone): implicating mechanisms of Th1 to Th2/Th3 immune-deviation. J Neuroimmunol 92 1/2 (1998) 113-121
43. Duda P.W., Schmied M.C., Cook S.L., Krieger J.I., and Hafler D.A. Glatiramer acetate (Copaxone) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis. J Clin Invest 105 7 (2000) 967-976
44. Teitelbaum D., Milo R., Arnon R., and Sela M. Synthetic copolymer 1 inhibits human T-cell lines specific for myelin basic protein. Proc Natl Acad Sci USA 89 1 (1992) 137-141
45. Gran B., Tranquill L.R., Chen M., Bielekova B., Zhou W., Dhib-Jalbut S., et al. Mechanisms of immunomodulation by glatiramer acetate. Neurology 55 11 (2000) 1704-1714
46. Aharoni R., Teitelbaum D., Leitner O., Meshorer A., Sela M., and Arnon R. Specific Th2 cells accumulate in the central nervous system of mice protected against experimental autoimmune encephalomyelitis by copolymer 1. Proc Natl Acad Sci USA 97 21 (2000) 11472-11477
47. Duda P.W., Krieger J.I., Schmied M.C., Balentine C., and Hafler D.A. Human and murine CD4 T cell reactivity to a complex antigen: recognition of the synthetic random polypeptide glatiramer acetate. J Immunol 165 12 (2000) 7300-7307
48. Neuhaus O., Farina C., Yassouridis A., Wiendl H., Then Bergh F., Dose T., et al. Multiple sclerosis: comparison of copolymer-1 reactive T cell lines from treated and untreated subjects reveals cytokine shift from Th1 to Th2. Proc Natl Acad Sci USA 97 13 (2000) 7452-7457
49. Chen M., Gran B., Costello K., Johnson K., Martin R., and Dhib-Jalbut S. Glatiramer acetate induces a Th2-biased response and cross reactivity with myelin basic protein in patients with MS. Mult Scler 7 4 (2001) 209-219
50. Sela M., and Teitelbaum D. Glatiramer acetate in the treatment of multiple sclerosis. Expert Opin Pharmacother 2 7 (2001) 1149-1165
51. Hohlfeld R. Therapeutic strategies in multiple sclerosis: immunotherapy. Philos Trans R Soc Lond B Biol Sci 354 1390 (1999) 1697-1710
52. Dhib-Jalbut S. Mechanisms of action of interferons and glatiramer acetate in multiple sclerosis. Neurology 58 8 Suppl. 4 (2002) S3-S9
53. Chen M., Valenzuela R.M., and Dhib-Jalbut S. Glatiramer acetate (GA)-reactive T-cells produce brain-derived neurotrophic factor. J Neurol Sci 215 1/2 (2003) 37-44
54. Ziemssen T., Kümpfel T., Klinkert W.E., Neuhaus O., and Hohlfeld R. Glatiramer acetate-specific T-helper 1- and 2-type cell lines produce BDNF: implications for multiple sclerosis therapy. Brain-derived neurotrophic factor. Brain 125 November (Pt 11) (2002) 2381-2391
55. Bornstein M.B., Miller A., Slagle S., Weitzman M., Crystal H., Drexler E., et al. A pilot trial of Cop 1 in exacerbating-remitting multiple sclerosis. N Engl J Med 317 7 (1987) 408-414
56. Johnson K.P., Brooks B.R., Cohen J.A., Ford C.C., Goldstein J., Lisak R.P., et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of phase III multicenter, double blind, placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology 45 7 (1995) 1268-1276
57. Johnson K.P., Brooks B.R., Cohen J.A., Ford C.C., Goldstein J., Lisak R.P., et al. Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. Neurology 50 3 (1998) 701-708
58. Johnson K.P., Brooks B.R., Ford C.C., Goodman A., Guarnaccia J., Lisak R.P., et al. Sustained clinical benefits of glatiramer acetate in relapsing remitting multiple sclerosis patients observed for 6 years. Copolymer 1 Multiple Sclerosis Study Group. Mult Scler 6 4 (2000) 255-266
59. Johnson K.P., Brooks B.R., Ford C.C., Goodman A., Lisak R.P., Meyers L.W., et al. Glatiramer acetate (Copaxone): comparison of continuous versus delayed therapy in a six-year organized multiple sclerosis trial. Mult Scler 9 6 (2003) 585-591
60. Johnson K.P., Ford C.C., Lisak R.P., and Wolinsky J.S. Neurologic consequence of delaying glatiramer acetate therapy for multiple sclerosis: 8-year data. Acta Neurol Scand 111 1 (2005) 42-47
61. Mancardi G.L., Sardanelli F., Parodi R.C., Melani E., Capello E., Inglese M., et al. Effect of copolymer-1 on serial gadolinium enhanced MRI in relapsing remitting multiple sclerosis. Neurology 50 4 (1998) 1127-1133
62. Comi G., Filippi M., and Wolinsky J.S. European/Canadian multicenter, double-blind, randomized, placebocontrolled 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 49 3 (2001) 290-297
63. Schellekens H. Bioequivalence and the immunogenicity of biopharmaceuticals. Nat Rev Drug Discov 1 6 (2002) 457-462
64. The IFNB Multiple Sclerosis Study Group, the University of British Columbia MS/MRI Analysis Group. Neutralizing antibodies during treatment of multiple sclerosis with interferon beta-lb: experience during the first three years. Neurology 47 4 (1996) 889-894
65. Malucchi S., Sala A., Gilli F., Bottero R., Di Sapio A., Capobianco M., et al. Neutralizing antibodies reduce the efficacy of beta-IFN during treatment of multiple sclerosis. Neurology 62 11 (2004) 2031-2037
66. Sominanda A., Rot U., Suoniemi M., Deisenhammer F., Hillert J., and Fogdell-Hahn A. Interferon beta preparations for the treatment of multiple sclerosis patients differ in neutralizing antibody seroprevalence and immunogenicity. Mult Scler 13 2 (2007) 208-214
67. Gneiss C., Tripp P., Reichartseder F., Egg R., Ehling R., Lutterotti A., et al. Differing immunogenic potentials of interferon beta preparations in multiple sclerosis patients. Mult Scler 12 6 (2006) 731-737
68. Deisenhammer F., Schellekens H., and Bertolotto A. Measurement of neutralizing antibodies to interferon beta in patients with multiple sclerosis. J Neurol 251 Suppl. 2 (2004) 1131-1139
69. Ross C., Clemmesen K.M., Svenson M., Sørensen P.S., Koch-Henriksen N., Skovgaard G.L., et al. Immunogenicity of interferon-beta in multiple sclerosis patients: influence of preparation, dosage, dose frequency, and route of administration. Danish Multiple Sclerosis Study Group. Ann Neurol 48 5 (2000) 706-712
70. Larocca A.P., Leung S.C., Marcus S.G., Colby C.B., and Borden E.C. Evaluation of neutralizing antibodies in patients treated with recombinant interferon-beta. J Interferon Res 9 Suppl. I (1989) S51-60
71. Bertolotto A., Deisenhammer F., Gallo P., and Sölberg Sørensen P. Immunogenicity of interferon beta: differences among products. J Neurol 251 Suppl. 2 (2004) 1115-1124
72. Jacobs L.D., Cookfair D.L., Rudick R.A., Herndon R.M., Richert J.R., Salazar A.M., et al. A phase III trial of intramuscular recombinant interferon beta as treatment for exacerbating-remitting multiple sclerosis; design and conduct of study and baseline characteristics of patients. Multiple Sclerosis Collaborative Research Group (MSCRG). Mult Scler 1 2 (1995) 118-135
73. Kappos L., Clanet M., Sandberg-Wollheim M., Radue E., Hartung H., Hohlfeld R., et al. Neutralizing antibodies and efficacy of interferon beta-la: a 4-year controlled study. Neurology 65 1 (2005) 40-47
74. Giovannoni G., Barbarash O., Casset-Semanaz F., King J., Metz L., Pardo G., et al. Safety and immunogenicity of a new formulation of interferon beta-1a (Rebif New Formulation) in a Phase IIIb study in patients with relapsing multiple sclerosis: 96-week results. Mult Scler 15 2 (2009) 219-228
75. Francis G.S., Rice G.P., Alsop J.C., and for the PRISMS (Prevention of Relapses and Disability by Interferon-1a Subcutaneously in Multiple Sclerosis) Study Group. Interferon beta-la in MS: results following development of neutralizing antibodies in PRISMS. Neurology 65 1 (2005) 48-55
76. Rice G.P.A., Paszner B., Oger J., Lesaux J., Paty D., and Ebers G. The evolution of neutralizing antibodies in multiple sclerosis patients treated with interferon beta-lb. Neurology 52 6 (1999) 1277-1279
77. Gneiss C., Reindl M., Lutterotti A., Ehling R., Egg R., Khalil M., et al. Interferon-beta: the neutralizing antibody (NAb) titre predicts reversion to NAb negativity. Mult Scler 10 5 (2004) 507-510
78. Polman C., Kappos L., White R., Dahlke F., Beckmann K., Pozzilli C., et al. Neutralizing antibodies during treatment of secondary progressive MS with interferon beta-1b. Neurology 60 1 (2003) 37-43
79. Panitch H., Miller A., Paty D., Weinshenker B., and North American Study Group on Interferon beta-1b in Secondary Progressive MS. Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study. Neurology 63 10 (2004) 1788-1795
80. Frank J.A., Richert N., Bash C., Stone L., Calabresi P.A., Lewis B., et al. Interferon-beta-1b slows progression of atrophy in RRMS: three-year follow-up in Nab- and Nab+ patients. Neurology 62 5 (2004) 719-725
81. Secondary Progressive Efficacy Clinical Trial of Recombinant Interferon beta 1a in MS (SPECTRIMS) Study Group. Randomized controlled trial of interferon-beta-1a in secondary progressive MS clinical results. Neurology 56 11 (2001) 1496-1504
82. Perini P., Calabrese M., Biasi G., and Gallo P. The clinical impact of interferon beta antibodies in relapsing-remitting MS. J Neurol 251 3 (2004) 305-309
83. Farrell R., Kapoor R., Leary S., Rudge P., Thompson A., Miller D., et al. Neutralizing anti-interferon beta antibodies are associated with reduced side effects and delayed impact on efficacy of interferon-beta. Mult Scler 14 2 (2008) 212-218
84. Malucchi S., Gilli F., Caldano M., Marnetto F., Valentino P., Granieri L., et al. Predictive markers for response to interferon therapy in patients with multiple sclerosis. Neurology 70 13 Pt 2 (2008) 1119-1127
85. Sorensen P.S., Ross C., Clemmesen K.M., Bendtzen K., Frederiksen J.L., Jensen K., et al. Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis. Lancet 362 9391 (2003) 1184-1191
86. Boz C., Oger J., Gibbs E., Grossberg S.E., and Neurologists of the UBC MS Clinic. Reduced effectiveness of long term interferon-beta treatment on relapses in neutralizing antibody-positive multiple sclerosis patients: a Canadian multiple sclerosis clinic-based study. Mult Scler 13 9 (2007) 1127-1137
87. Sorensen P.S., Deisenhammer F., Duda P., Hohlfeld R., Myhr K.M., Palace J., et al. Guidelines on use of anti-IFN-beta antibody measurements in multiple sclerosis: report of an EFNS Task Force on IFN-beta antibodies in multiple sclerosis. Eur J Neurol 12 11 (2005) 817-827
88. Goodin D.S., Frohman E.M., Hurwitz B., O'Connor P.W., Oger J.J., Reder A.T., 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 68 13 (2007) 977-984
89. Giovannoni G., and Goodman A. Neutralizing anti-IFN-beta antibodies: how much more evidence do we need to use them in practice?. Neurology 65 July (1) (2005) 6-8
90. Teitelbaum D., Brenner T., Abramsky O., Aharoni R., Sela M., and Arnon R. Antibodies to glatiramer acetate do not interfere with its biological functions and therapeutic efficacy. Mult Scler 9 6 (2003) 592-599
91. Salama H.H., Hong J., Zang Y.C., El-Mongui A., and Zhang J. Blocking effects of serum reactive antibodies induced by glatiramer acetate treatment in multiple sclerosis. Brain 126 Pt 12 (2003) 2638-2647
92. Karussis D., Teitelbaum D., Sicsic C., Brenner T., and the AC001 multi-center Israeli study group. Long-term treatment of multiple sclerosis with glatiramer acetate: natural history of the subtypes of anti-glatiramer acetate antibodies and their correlation with clinical efficacy. J Neuroimmunol (2010) February 12 [Epub ahead of print]
93. Freedman M.S., Hughes B., Mikol D.D., Bennett R., Cuffel B., Divan V., et al. Efficacy of disease-modifying therapies in relapsing remitting multiple sclerosis: a systematic comparison. Eur Neurol 60 1 (2008) 1-11
94. Mikol D.D., Barkhof F., Chang P., Coyle P.K., Jeffery D.R., Schwid S.R., 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 7 10 (2008) 903-914
95. Wolansky L., Cook S., Skurnick J., Lincoln J., Tulloch K., Franco P., et al. Betaseron vs. Copaxone in MS with triple-dose gadolinium and 3-T MRI Endpoints (BECOME): announcement of final primary study outcome. Mult Scler 13 Suppl. 2 (2007) P206
96. Cadavid D., Wolansky L., Cook S., Halper J., Hill J., Younes M., et al. Betaseron versus copaxone in multiple sclerosis with triple-dose gadolinium and 3 Tesla MRI Endpoints (BECOME): announcement of secondary clinical outcomes. Mult Scler 13 Suppl. 2 (2007) P207
97. ® Efficacy Yielding Outcomes of a New Dose) study. Neurology 70 11; Late Breaking Science Supplement (2008) S004
98. ® treatments in relapsing remitting multiple sclerosis. J Neurol 255 Suppl. 2 (2008) 9
99. Lenk H., Muller U., and Tanneberger S. Mitoxantrone: mechanism of action, antitumor activity, pharmacokinetics, efficacy in the treatment of solid tumors and lymphomas, and toxicity. Anticancer Res 7 6 (1987) 1257-1264
100. Rosenberg L.S., Carvlin M.J., and Krugh T.R. The antitumor agent mitoxantrone binds cooperatively to DNA: evidence for heterogeneity in DNA conformation. Biochemistry 25 5 (1986) 1002-1008
101. Fidler J.M., DeJoy S.Q., and Gibbons Jr. J.J. Selective immunomodulation by the antineoplastic agent mitoxantrone. I. Suppression of B lymphocyte function. J Immunol 137 2 (1986) 727-732
102. Fidler J.M., DeJoy S.Q., Smith III F.R., and Gibbons Jr. J.J. Selective immunomodulation by the antineoplastic agent mitoxantrone. II. Nonspecific adherent suppressor cells derived from mitoxantrone treated mice. J Immunol 136 8 (1986) 2747-2754
103. Bellosillo B., Colomer D., Pons G., and Gil J. Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol 100 1 (1998) 142-146
104. Weilbach F.X., Chan A., Toyka K.V., and Gold R. Mitoxantrone-induced immunological changes in MS patients-ex vivo studies on proliferation and cell death of peripheral blood leukocytes. J Neurol 249 Suppl. 1 (2002) 113
105. Millefiorini E., Gasperini C., Pozzilli C., D'Andrea F., Bastianello S., Trojano M., et al. Randomized placebo-controlled trial of mitoxantrone in relapsing remitting multiple sclerosis: 24-month clinical and MRI outcome. J Neurol 244 3 (1997) 153-159
106. Edan G., Miller D., Clanet M., Confavreux C., Lyon-Caen O., Lubetzki C., et al. Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomized multicentre study of active disease using MRI and clinical criteria. J Neurol Neurosurg Psychiatry 62 2 (1997) 112-118
107. Hartung H.P., Gonsette R., Konig N., Kwiecinski H., Guseo A., Morrissey S.P., et al. Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet 360 9350 (2002) 2018-2025
108. Debouverie M., Vandenberghe N., Morrissey S.P., Anxionnat R., Pittion-Vouyovitch S., Vespignani H., et al. Predictive parameters of mitoxantrone effectiveness in the treatment of multiple sclerosis. Mult Scler 10 4 (2004) 407-412
109. Edan G., Morrissey S.P., and Hartung H.P. Use of mitoxantrone to treat multiple sclerosis. In: Cohen J.A., and Rudick R.A. (Eds). Multiple sclerosis therapeutics. 2nd ed. (2003), Martin Dunitz, London, UK 403-427
110. Crossley R.J. Clinical safety and tolerance of mitoxantrone. Semin Oncol 11 3 Suppl. 1 (1984) 54-58
111. Dukart G., and Barone J.S. An overview of cardiac episodes following mitoxantrone administration. Cancer Treat Symp 3 (1984) 35-41
112. Gams R.A., and Wesler M.J. Mitoxantrone cardiotoxicity: results from Southeastern Cancer Study Group. Cancer Treat Symp 3 (1984) 31-33
113. Foster B.J., Lev L., Bergemann C., and Marsoni S. Cardiac events in phase II trials with mitoxantrone. Cancer Treat Symp 3 (1984) 43-46
114. Posner L.E., Dukart G., Goldberg J., Bernstein T., and Cartwright K. Mitoxantrone: an overview of safety and toxicity. Invest New Drugs 3 2 (1985) 123-132
115. Fountzilas G., Afthonidis D., Geleris P., Salem N., Kottas G., Halkidis C., et al. Cardiotoxicity evaluation in patients treated with a mitoxantrone combination as adjuvant chemotherapy for breast cancer. Anticancer Res 12 1 (1992) 231-234
116. Mauch E., Eisenmann S., Hahn A., Zenker O., Rubin A., and Ghalie R. Mitoxantrone in the treatment of patients with multiple sclerosis: a large single center experience. Mult Scler 5 Suppl. 1 (1999) P366
117. Ghalie R.G., Edan G., Laurent M., Mauch E., Eisenman S., Hartung H.P., et al. Cardiac adverse effects associated with mitoxantrone (Novantrone) therapy in patients with MS. Neurology 59 6 (2002) 909-913
118. Feuillet L., Guedj E., Eusebio A., Malikova I., Pelletier J., Mundler O., et al. Acute heart failure in a patient treated by mitoxantrone for multiple sclerosis. Rev Neurol (Paris) 159 12 (2003) 1169-1172
119. Edan G., Brochet B., Clanet M., Clavelou P., Confavreux C., Debouverie M., et al. Safety profile of mitoxantrone in a cohort of 802 multiple sclerosis patients: a 4-year mean follow-up study. Neurology 62 Suppl. 5 (2004) A493
120. Vicari A.M., Ciceri F., Folli F., Lanzi R., Colombo B., Comi G., et al. Acute promyelocytic leukemia following mitoxantrone as single agent for the treatment of multiple sclerosis. Leukemia 12 3 (1998) 441-442
121. Ghalie R.G., Mauch E., Edan G., Hartung H.P., Gonsette R.E., Eisenmann S., et al. A study of therapy-related acute leukaemia after mitoxantrone therapy for multiple sclerosis. Mult Scler 8 5 (2002) 441-445
122. Cattaneo C., Almici C., Borlenghi E., Motta M., and Rossi G. A case of acute promyelocytic leukaemia following mitoxantrone treatment of multiple sclerosis. Leukemia 17 5 (2003) 985-986
123. Mogenet I., Simiand-Erdociain E., Canonge J.M., and Pris J. Acute myelogenous leukemia following mitoxantrone treatment for multiple sclerosis. Ann Pharmacother 37 5 (2003) 747-748
124. Heesen C., Bruegmann M., Gbdamosi J., Koch E., Mönch A., and Buhmann C. Therapy-related acute myelogenous leukaemia (t-AML) in a patient with multiple sclerosis treated with mitoxantrone. Mult Scler 9 2 (2003) 213-214
125. Jaster J.H., Niell H.B., Dohan Jr. F.C., and Smith T.W. Therapy-related acute myeloblastic leukemia after mitoxantrone treatment in a patient with MS. Neurology 60 8 (2003) 1399-1400
126. Brassat D., Recher C., Waubant E., Le Page E., Rigal-Huguet F., Laurent G., et al. Therapy-related acute myeloblastic leukemia after mitoxantrone treatment in a patient with MS. Neurology 59 6 (2002) 954-955
127. Bines J., Oleske D.M., and Cobleigh M.A. Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer. J Clin Oncol 14 5 (1996) 1718-1729
128. Meistrich M.L., Wilson G., Mathur K., Fuller L.M., Rodriguez M.A., McLaughlin P., et al. Rapid recovery of spermatogenesis after mitoxantrone, vincristine, vinblastine, and prednisone chemotherapy for Hodgkin's disease. J Clin Oncol 15 12 (1997) 3488-3495
129. http://www.fda.gov/cder/drug/infopage/natalizumab/default.htm
130. Engelhardt B., and Kappos L. Natalizumab: targeting alpha4-integrins in multiple sclerosis. Neurodegener Dis 5 1 (2008) 16-22
131. Johnson K.P. Natalizumab (Tysabri) treatment for relapsing multiple sclerosis. Neurologist 13 4 (2007) 182-187
132. Rice G.P., Hartung H.P., and Calabresi P.A. Anti-alpha4 integrin therapy for multiple sclerosis: mechanisms and rationale. Neurology 64 8 (2005) 1336-1342
133. Miller D.H., Khan O.A., Sheremata W.A., Blumhardt L.D., Rice G.P., Libonati M.A., et al. A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 348 1 (2003) 15-23
134. Tubridy N., Behan P.O., Capildeo R., Chaudhuri A., Forbes R., Hawkins C.P., et al. The effect of anti-alpha4 integrin antibody on brain lesion activity in MS. The UK Antegren Study Group. Neurology 53 3 (1999) 466-472
135. Polman C.H., O'Connor P.W., Havrdova E., Hutchinson M., Kappos L., Miller D.H., et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354 9 (2006) 899-910
136. Rudick R.A., Stuart W.H., Calabresi P.A., Confavreux C., Galetta S.L., Radue E.W., et al. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 354 9 (2006) 911-923
137. Rudick R.A., and Sandrock A. Natalizumab: alpha 4-integrin antagonist selective adhesion molecule inhibitors for MS. Expert Rev Neurother 4 4 (2004) 571-580
138. Kleinschmidt-DeMasters B.K., and Tyler K.L. Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med 353 4 (2005) 369-374
139. Langer-Gould A., Atlas S.W., Green A.J., Bollen A.W., and Pelletier D. Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med 353 4 (2005) 375-381
140. Van Assche G., Van Ranst M., Sciot R., Dubois B., Vermeire S., Noman M., et al. Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn's disease. N Engl J Med 353 4 (2005) 362-368
141. Chen Y., Bord E., Tompkins T., Miller J., Tan C.S., Kinkel R.P., et al. Asymptomatic reactivation of JC virus in patients treated with natalizumab. N Engl J Med 361 11 (2009) 1067-1074
142. Calabresi P.A., Giovannoni G., Confavreux C., Galetta S.L., Havrdova E., Hutchinson M., et al. The incidence and significance of anti-natalizumab antibodies: results from AFFIRM and SENTINEL. Neurology 69 14 (2007) 1391-1403
143. Karussis D.M., Slavin S., Lehmann D., Mizrachi-Koll R., Abramsky O., and Ben-Nun A. Prevention of experimental autoimmune encephalomyelitis and induction of tolerance with acute immunosuppression followed by syngeneic bone marrow transplantation. J Immunol 148 6 (1992) 1693-1698
144. Burt R.K., Slavin S., Burns W.H., and Marmont A.M. Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: getting closer to a cure?. Blood 99 3 (2002) 768-784
145. Fassas A., Anagnostopoulos A., Kazis A., Kapinas K., Sakellari I., Kimiskidis V., et al. Autologous stem cell transplantation in progressive multiple sclerosis - an interim analysis of efficacy. J Clin Immunol. 20 1 (2000) 24-30
146. Fassas A., Passweg J.R., Anagnostopoulos A., Kazis A., Kozak T., Havrdova E., et al. Hematopoietic stem cell transplantation for multiple sclerosis: a retrospective multicenter study. J Neurol 249 8 (2002) 1088-1097
147. Sykes M., and Nikolic B. Treatment of severe autoimmune disease by stem-cell transplantation. Nature 435 7042 (2005) 620-627
148. Griffith L.M., Pavletic S.Z., Tyndall A., Bredeson C.N., Bowen J.D., Childs R.W., et al. Feasibility of allogeneic hematopoietic stem cell transplantation for autoimmune disease: position statement from a National Institute of Allergy and Infectious Diseases and National Cancer Institute-sponsored international workshop, Bethesda, MD, March 12 and 13, 2005. Biol Blood Marrow Transplant 11 11 (2005) 862-870
149. Diaconescu R., Flowers C.R., Storer B., Sorror M.L., Maris M.B., Maloney D.G., et al. Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors. Blood 104 5 (2004) 1550-1558
150. Openshaw H., Stuve O., Antel J.P., Nash R., Lund B.T., Weiner L.P., et al. Multiple sclerosis flares associated with recombinant granulocyte colony-stimulating factor. Neurology 54 11 (2000) 2147-2150
151. Nash R.A., Bowen J.D., McSweeney P.A., Pavletic S.Z., Maravilla K.R., Park M.S., et al. High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis. Blood 102 7 (2003) 2364-2372
152. Mancardi G., and Saccardi R. Autologous haematopoietic stem-cell transplantation in multiple sclerosis. Lancet Neurol 7 7 (2008) 626-636
153. Fassas A., Anagnostopoulos A., Kazis A., Kapinas K., Sakellari I., Kimiskidis V., et al. Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first results of a pilot study. Bone Marrow Transplant 20 8 (1997) 631-638
154. Kozák T., Havrdová E., Pit'ha J., Gregora E., Pytlík R., Maaloufová J., et al. High-dose immunosuppressive therapy with PBPC support in the treatment of poor risk multiple sclerosis. Bone Marrow Transplant 25 5 (2000) 525-531
155. Kozák T., Havrdová E., Pit'ha J., Gregora E., Pytlík R., Maaloufová J., et al. Immunoablative therapy with autologous stem cell transplantation in the treatment of poor risk multiple sclerosis. Transplant Proc 33 3 (2001) 2179-2181
156. Su L., Xu J., Ji B.X., Wan S.G., Lu C.Y., Dong H.Q., et al. Autologous peripheral blood stem cell transplantation for severe multiple sclerosis. Int J Hematol 84 3 (2006) 276-281
157. Xu J., Ji B.X., Su L., Dong H.Q., Sun X.J., and Liu C.Y. Clinical outcomes after autologous haematopoietic stem cell transplantation in patients with progressive multiple sclerosis. Chin Med J (Engl) 119 22 (2006) 1851-1855
158. Burt R.K., Cohen B.A., Russel E., Spero K., Joshi A., Oyama Y., et al. Hematopoietic stem cell transplantation for progressive multiple sclerosis: failure of intense immune suppression to prevent disease progression in patients with high disability scores. Blood 102 7 (2003) 2373-2378
159. Samijn J.P., te Boekhorst P.A., Mondria T., van Doorn P.A., Flach H.Z., van der Meché F.G., et al. Intense T cell depletion followed by autologous bone marrow transplantation for severe multiple sclerosis. J Neurol Neurosurg Psychiatry 77 1 (2006) 46-50
160. Openshaw H., Lund B.T., Kashyap A., Atkinson R., Sniecinski I., Weiner L.P., et al. Peripheral blood stem cell transplantation in multiple sclerosis with busulfan and cyclophosphamide conditioning: report of toxicity and immunological monitoring. Biol Blood Marrow Transplant 6 5A (2000) 563-575
161. Carreras E., Saiz A., Marin P., Martínez C., Rovira M., Villamor N., et al. CD34+ selected autologous peripheral blood stem cell transplantation for multiple sclerosis: report of the toxicity and treatment results at one year of follow-up in 15 patients. Haematologica 88 3 (2003) 306-314
162. Saiz A., Blanco Y., Carreras E., Berenguer J., Rovira M., Pujol T., et al. Clinical and MRI outcome after autologous hemtopoietic stem cell transplantation in MS. Neurology 62 2 (2004) 282-284
163. Loh S.M., Ratnagopal P., Tan H.C., Goh Y.T., Koh B.C., Koh L.P., et al. Successful autologous hematopoietic stem cell transplantations for severe multiple sclerosis with fludarabine and cyclophosphamide conditioning. Int J Hematol 83 4 (2006) 368-369
164. Gualandi F., Bruno B., Van Lint M.T., Luchetti S., Uccelli A., Capello E., et al. Autologous stem cell transplantation for severe autoimmune diseases: a 10-year experience. Ann NY Acad Sci 1110 (2007) 455-464
165. Mancardi G.L., Saccardi R., Filippi M., Gualandi F., Murialdo A., Inglese M., et al. Autologous hematopoietic stem cell transplantation suppresses Gd-enhanced MRI activity in MS. Neurology 57 1 (2001) 62-68
166. Saccardi R., Mancardi G.L., Solari A., Bosi A., Bruzzi P., Di Bartolomeo P., et al. Autologous HSCT for severe progressive multiple sclerosis in a multicenter trial: impact on disease activity and quality of life. Blood 105 6 (2005) 2601-2607
167. Ni X.S., Ouyang J., Zhu W.H., Wang C., and Chen B. Autologous hematopoietic stem cell transplantation for progressive multiple sclerosis: report of efficacy and safety at three yr of follow up in 21 patients. Clin Transplant 20 4 (2006) 485-489
168. Atkins H., and Freedman M.S. Immunoablative therapy as a treatment aggressive multiple sclerosis. Neurol Clin 23 1 (2005) 273-300 ix
169. Freedman M.S. Bone marrow transplantation: does it stop MS progression?. J Neurol Sci 259 1/2 (2007) 85-89
170. Saccardi R., Kozak T., Bocelli-Tyndall C., Fassas A., Kazis A., Havrdova E., et al. Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database. Mult Scler 12 6 (2006) 814-823
171. Mancardi G.L., Murialdo A., Rossi P., Gualandi F., Martino G., Marmont A., et al. Autologous stem cell transplantation as rescue therapy in malignant forms of multiple sclerosis. Mult Scler 11 3 (2005) 367-371
172. Havrdova E. Aggressive multiple sclerosis-is there a role for stem cell transplantation?. J Neurol 252 Suppl. 3 (2005) iii34-iii37
173. Kimiskidis V., Sakellari I., Tsimourtou V., Kapina V., Papagiannopoulos S., Kazis D., et al. Autologous stem-cell transplantation in malignant multiple sclerosis: a case with a favorable long-term outcome. Mult Scler 14 2 (2008) 278-283
174. Fagius J., Lundgren J., and Oberg G. Early highly aggressive MS successfully treated by hematopoietic stem cell transplantation. Mult Scler 15 February (2) (2009) 229-237
175. Matthews W.B. Clinical aspects. Course and prognosis. In: Matthews W.B. (Ed). McAlpine's multiple sclerosis. second ed. (1991), Churchill Livingstone, Edinburgh 139-163
176. Rodriguez M., Karnes W.E., Bartleson J.D., and Pineda A.A. Plasmapheresis in acute episodes of fulminant CNS inflammatory demyelinaion. Neurology 43 10 (1993) 1100-1104
177. Monaca C., Stoijkovic T., de Seze J., Ruchoux M.M., Pruvo J.P., and Vermersch P. Fulminant multiple sclerosis. Rev Neurol (Paris) 156 2 (2000) 180-181
178. Silani V., and Cova L. Stem cell transplantation in multiple sclerosis: safety and ethics. J Neurol Sci 265 1/2 (2008) 116-121
179. Zappia E., Casazza S., Pedemonte E., Benvenuto F., Bonanni I., Gerdoni E., et al. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood 106 5 (2005) 1755-1761
180. Di Nicola M., Carlo-Stella C., Magni M., Milanesi M., Longoni P.D., Matteucci P., et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99 10 (2002) 3838-3843
181. Zhao R.C., Liao L., and Han Q. Mechanisms of and perspectives on the mesenchymal stem cells in immunotherapy. J Lab Clin Med 143 5 (2003) 284-291
182. Le Blanc K., Rasmusson I., Sundberg B., Götherström C., Hassan M., Uzunel M., et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal cells. Lancet 363 9419 (2004) 1439-1441
183. Freedman M.S., Bar-Or A., Atkins H.L., Karussis D., Frassoni F., Lazarus H., et al. The therapeutic potential of mesenchymal stem cell transplantation as a treatment for multiple sclerosis: consensus report of the International MSCT Study Group. Mult Scler (2010) January 19 [Epub ahead of print]
184. Filippi M., Rovaris M., Inglese M., Barkhof F., De Stefano N., Smith S., et al. Interferon beta-1a for brain tissue loss in patients at presentation with syndromes suggestive of multiple sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet 364 9444 (2004) 1489-1496
185. Paolillo A., Piattella M.C., Pantano P., Di Legge S., Caramia F., Russo P., et al. The relationship between inflammation and atrophy in clinically isolated syndromes suggestive of multiple sclerosis. A monthly MRI study after triple-dose gadolinium-DTPA. J Neurol 251 4 (2004) 432-439
186. Brex P.A., Leary S.M., O'Riordan J.I., Miszkiel K.A., Plant G.T., Thompson A.J., et al. Measurement of spinal cord area in clinically isolated syndromes suggestive of multiple sclerosis. Neurol Neurosurg Psychiatry 70 4 (2001) 544-547
187. Comi G., Martinelli V., Rodegher M., Moiola L., Bajenaru O., Carra A., 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 374 9700 (2009) 1503-1511
188. Comi G., Filippi M., Barkhof F., Durelli L., Edan G., Fernández O., et al. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 357 9268 (2001) 1576-1582
189. Jacobs L.D., Beck R.W., Simon J.H., Kinkel R.P., Brownscheidle C.M., Murray T.J., et al. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. N Engl J Med 343 13 (2000) 898-904
190. Kappos L., Polman C.H., Freedman M.S., Edan G., Hartung H.P., Miller D.H., et al. Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology 67 7 (2006) 1242-1249
191. Kappos L., Freedman M.S., Polman C.H., Edan G., Hartung H.P., Miller D.H., et al. Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study. Lancet 370 9585 (2007) 389-397
192. McDonald W.I., Compston A., Edan G., Goodkin D., Hartung H.P., Lublin F.D., et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the Diagnosis of Multiple Sclerosis. Ann Neurol 50 1 (2001) 121-127
193. ClinicalTrials.gov. http://clinicaltrials.gov. Accessed January 19; 2010.
194. Langer-Gould A., Popat R.A., Huang S.M., Cobb K., Fontoura P., Gould M.K., et al. Clinical and demographic predictors of long-term disability in patients with relapsing remitting multiple sclerosis: a systematic review. Arch Neurol 63 12 (2006) 1686-1691
195. Fisniku L.K., Brex P.A., Altmann D.R., Miszkiel K.A., Benton C.E., Lanyon R., et al. Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. Brain 131 Pt 3 (2008) 808-817
196. Miller J.R. The importance of early diagnosis of multiple sclerosis. J Manag Care Pharm 10 3 Suppl. B (2004) S4-S11
197. Kantarci, et al. Prognostic factors in multiple sclerosis. In: Cook S.D. (Ed). Handbook of Multiple Sclerosis. 3rd ed. (2001), Marcel Dekker, New York 449-463
198. Scott T.F., Schramke C.J., and Cutter G. Sample size estimates for determining treatment effects in high-risk patients with early relapsing remitting multiple sclerosis. Mult Scler 9 3 (2003) 289-292
199. Bashir K., Buchwald L., Coyle P., et al. MS patient management: optimizing immunomodulatory therapy for MS patients. Int J MS Care June (Suppl.) (2002) 1-7
200. Cohen B.A., Khan O., Jeffery D.R., Bashir K., Rizvi S.A., Fox E.J., et al. Identifying and treating patients with suboptimal responses. Neurology 63 12 Suppl. 6 (2004) S33-S40
201. Freedman M.S., Patry D.G., Grand'Maison F., Myles M.L., Paty D.W., Selchen D.H., et al. Treatment optimization in multiple sclerosis. Can J Neurol Sci 31 2 (2004) 157-168
202. International Working Group for Treatment Optimization in MS. Treatment optimization in multiple sclerosis: report of an international consensus meeting. Eur J Neurol 11 1 (2004) 43-47
203. Freedman M.S., and Forrestal F.G. Canadian treatment optimization recommendations (TOR) as a predictor of disease breakthrough in patients with multiple sclerosis treated with interferon beta-1a: analysis of the PRISMS study. Mult Scler 14 9 (2008) 1234-1241
204. Ruiz-Peña J.L., Duque P., and Izquierdo G. Optimization of treatment with interferon beta in multiple sclerosis. Usefulness of automatic system application criteria. BMC Neurol 8 (2008) 3
205. Karussis D., Biermann L.D., Bohlega S., Boiko A., Chofflon M., Fazekas F., et al. A recommended treatment algorithm in relapsing multiple sclerosis: report of an international consensus meeting. Eur J Neurol 13 1 (2006) 61-71
206. Stuart W.H. Clinical management of multiple sclerosis: the treatment paradigm and issues of patient management. J Manag Care Pharm 10 3 Suppl. b (2004) S19-S25
207. Rich S.R., Coleman I.C., Cook R., Hum D.S., Johnson B., Maves T., et al. Stepped-care approach to treating MS: a managed care treatment algorithm. J Manage Care Pharm 10 3 Suppl. B (2004) S26-S32
208. Rieckmann P., Toyka K.V., Bassetti C., Beer K., Beer S., Buettner U., et al. Escalating immunotherapy of multiple sclerosis-new aspects and practical application. J Neurol 251 11 (2004) 1329-1339
209. Durelli L., Barbero P., Bergui M., Versino E., Bassano M.A., Verdun E., et al. The optimization of interferon for MS Study: 375 micrograms interferon beta-1b in suboptimal responders. J Neurol 255 9 (2008) 1315-1323
210. Caon C., Din M., Ching W., Tselis A., Lisak R., and Khan O. Clinical course after change of immunomodulating therapy in relapsing-remitting multiple sclerosis. Eur J Neurol 13 5 (2006) 471-474
211. Carrá A., Onaha P., Luetic G., Burgos M., Crespo E., Deri N., et al. Therapeutic outcome 3 years after switching of immunomodulatory therapies in patients with relapsing-remitting multiple sclerosis in Argentina. Eur J Neurol 15 4 (2008) 386-393
212. Gajofatto A., Bacchetti P., Grimes B., High A., and Waubant E. Switching first-line disease-modifying therapy after failure: impact on the course of relapsing-remitting multiple sclerosis. Mult Scler 15 1 (2009) 50-58
213. Téllez N., Río J., Tintoré M., et al. Mitoxantrone in MS patients, non-responders to interferon. 21st Congress of the European Committee for the Treatment and Research in Multiple Sclerosis. September 28-October 1, Madrid, Spain (2005)
214. Correale J., Rush C., Amengual A., and Goicochea M.T. Mitoxantrone as rescue therapy in worsening relapsing-remitting MS patients receiving IFN-beta. J Neuroimmunol 162 1/2 (2005) 173-183
215. Gladstone D.E., Zamkoff K.W., Krupp L., Peyster R., Sibony P., Christodoulou C., et al. High-dose cyclophosphamide for moderate to severe refractory multiple sclerosis. Arch Neurol 63 10 (2006) 1388-1393
216. Conway D., and Cohen J.A. Combination therapy in multiple sclerosis. Lancet Neurol 9 3 (2010 Mar) 299-308
217. Cohen J.A., Calabresi P.A., Chakraborty S., Edwards K.R., Eickenhorst T., Felton III W.L., et al. Avonex Combination Trial in relapsing-remitting MS: rationale, design and baseline data. Mult Scler 14 3 (2008) 370-382
218. Cohen J.A., Imrey P.B., Calabresi P.A., Edwards K.R., Eickenhorst T., Felton III W.L., et al. Results of the Avonex Combination Trial (ACT) in relapsing-remitting MS. Neurology 72 6 (2009) 535-541
219. Freedman M.S. Induction vs. escalation of therapy for relapsing multiple sclerosis: the evidence. Neurol Sci 29 Suppl. 2 (2008) S250-S252
220. ® (mitoxantrone for injection concentrate) (2006), Full Prescribing Information, EMD Serono, Inc., Rockland, MA
221. ® (natalizumab) (2008), Full Prescribing Information, Biogen Idec Inc., Cambridge, MA
222. The European Study Group on Interferon Beta-1b in Secondary Progressive MS. Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. Lancet 352 9139 (1998) 1491-1497
223. Cohen J.A., Goodman A.D., Heidenreich F.R., et al. Results of IMPACT, a phase 3 trial of interferon beta-1a in secondary progressive MS. Neurology 56 Suppl. 3 (2001) A148-A149
224. Goodin D.S., Frohman E.M., Garmany Jr. G.P., Halper J., Likosky W.H., Lublin F.D., et al. Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology 58 2 (2002) 169-178
225. Teitelbaum D., Arnon R., and Sela M. Copolymer-1: from basic research to clinical application. Cell Mol Life Sci 53 1 (1997) 24-28
226. Leary S.M., Miller D.H., Stevenson V.L., Brex P.A., Chard D.T., and Thompson A.J. Interferon beta-1a in primary progressive MS: an exploratory, randomized, controlled trial. Neurology 60 1 (2003 Jan 14) 44-51
227. Montalban X., Sastre-Garriga J., Tintoré M., Brieva L., Aymerich F.X., Río J., et al. A single-center, randomized, double-blind, placebo-controlled study of interferon beta-1b on primary progressive and transitional multiple sclerosis. Mult Scler 15 10 (2009) 1195-1205
228. Montalban X. Overview of European pilot study of interferon beta-Ib in primary progressive multiple sclerosis. Mult Scler 10 Suppl. 1 (2004) S62 discussion 62-64
229. Leary S.M., and Thompson A.J. Interferon beta-1a in primary progressive multiple sclerosis. J Neurol Sci 5 2 (2003) 215-216 206
230. Wolinsky J.S., Narayana P.A., O'connor P., Coyle P.K., Ford C., Johnson K., et al. Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol 61 1 (2007) 14-24
231. Kita M., Cohen J.A., Fox R.J., Evangelista E., Pelletier D., Stone J., et al. A phase II trial of mitoxantrone in patients with primary progressive multiple sclerosis (abstract S12.004). 56th annual meeting of the American Academy of Neurology. San Francisco, USA (2004)
232. British and Dutch Multiple Sclerosis Azathioprine Trial Group. Double-masked trial of azathioprine in multiple sclerosis. Lancet 2 8604 (1988) 179-183
233. Goodkin D.E., Rudick R.A., VanderBrug Medendorp S., Daughtry M.M., Schwetz K.M., Fischer J., et al. Low dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis. Ann Neurol 37 1 (1995) 30-40
234. Rice G.P.A., Filippi M., Comi G., and Cladribine MRI Study Group. Cladribine and progressive MS. clinical and MRI outcomes of a multicenter controlled trial. Neurology 54 5 (2000) 1145-1155
235. Pöhlau D., Przuntek H., Sailer M., Bethke F., Koehler J., König N., et al. Intravenous immunoglobulin in primary and secondary chronic progressive multiple sclerosis: a randomized placebo controlled multicentre study. Mult Scler 13 9 (2007) 1107-1117
236. Kalkers N.F., Barkhof F., Bergers E., van Schijndel R., and Polman C.H. The effect of the neuroprotective agent riluzole on MRI parameters in primary progressive multiple sclerosis: a pilot study. Mult Scler 8 6 (2002) 532-533
237. Matloubian M., Lo C.G., Cinamon G., Lesneski M.J., Xu Y., Brinkmann V., et al. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427 6972 (2004) 355-360
238. Chiba K. FTY720, a new class of immunomodulator, inhibits lymphocyte egress from secondary lymphoid tissues and thymus by agonistic activity at sphingosine 1-phosphate receptors. Pharmacol Ther 108 3 (2005) 308-319
239. Massberg S., and Von Andrian U.H. Fingolimod and sphingosine-1-phosphate-modifiers of lymphocyte migration. N Engl J Med 355 11 (2006) 1088-1091
240. Dev K.K., Mullershausen F., Mattes H., Kuhn R.R., Bilbe G., Hoyer D., et al. Brain sphingosine-1-phosphate receptors: implications for FTY720 in the treatment of multiple sclerosis. Pharmacol Ther 117 1 (2008) 77-93
241. Budde K., Schmouder R.L., Brunkhorst R., Nashan B., Lücker P.W., Mayer T., et al. First human trial of FTY720, a novel immunomodulator, in stable renal transplant patients. J Am Soc Nephrol 13 4 (2002) 1073-1083
242. Fujino M., Funeshima N., Kitazawa Y., Kimura H., Amemiya H., Suzuki S., et al. Amelioration of experimental autoimmune encephalomyelitis in Lewis rats by FTY720 treatment. J Pharmacol Exp Ther 305 1 (2003) 70-77
243. Rausch M., Hiestand P., Foster C.A., Baumann D.R., Cannet C., and Rudin M. Predictability of FTY720 efficacy in experimental autoimmune encephalomyelitis by in vivo macrophage tracking: clinical implications for ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging. J Magn Reson Imaging 20 1 (2004) 16-24
244. Webb M., Tham C.S., Lin F.F., Lariosa-Willingham K., Yu N., Hale J., et al. Sphingosine 1-phosphate receptor agonists attenuate relapsing-remitting experimental autoimmune encephalitis in SJL mice. J Neuroimmunol 153 1 (2004) 108-121
245. Kappos L., Antel J., Comi G., Montalban X., O'Connor P., Polman C.H., et al. Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med 355 11 (2006) 1124-1140
246. O'Connor P., Comi G., Montalban X., Antel J., Radue E.W., de Vera A., et al. Oral fingolimod (FTY720) in multiple sclerosis: two-year results of a phase II extension study. Neurology 72 1 (2009) 73-79
247. Kappos L., Radue E.W., O'Connor P., Polman C., Hohlfeld R., Calabresi P., et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 362 5 (2010) 387-401
248. Cohen J.A., Barkhof F., Comi G., Hartung H.P., Khatri B.O., Montalban X., et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 362 5 (2010) 402-415
249. Leypoldt F., Münchau A., Moeller F., Bester M., Gerloff C., and Heesen C. Hemorrhaging focal encephalitis under fingolimod (FTY720) treatment: a case report. Neurology 72 11 (2009) 1022-1024
250. Beutler E. Cladribine (2-chlorodeoxyadenosine). Lancet 340 8825 (1992) 952-956
251. Brousil J.A., Roberts R.J., and Schlein A.L. Cladribine: an investigational immunomodulatory agent for multiple sclerosis. Ann Pharmacother 40 10 (2006) 1814-1821
252. Beutler E., Sipe J.C., Romine J.S., Koziol J.A., McMillan R., and Zyroff J. The treatment of chronic progressive multiple sclerosis with cladribine. Proc Natl Acad Sci USA 93 4 (1996) 1716-1720
253. Romine J.S., Sipe J.C., Koziol J.A., Zyroff J., and Beutler E. A double-blind, placebo-controlled, randomized trial of cladribine in relapsing-remitting multiple sclerosis. Proc Assoc Am Phys 111 1 (1999) 35-44
254. Sipe J.C., Romine J.S., Koziol J.A., McMillan R., Zyroff J., and Beutler E. Cladribine in treatment of chronic progressive multiple sclerosis. Lancet 344 8914 (1994) 9-13
255. Sipe J.C., Romine J.S., Koziol J.A., McMillan R., Zyroff J., and Beutler E. Development of cladribine treatment in multiple sclerosis. Mult Scler 1 6 (1996) 343-347
256. Filippi M., Rovaris M., Iannucci G., Mennea S., Sormani M.P., and Comi G. Whole brain volume changes in patients with progressive MS treated with cladribine. Neurology 55 11 (2000) 1714-1718
257. Filippi M., Rovaris M., Rice G.P., Sormani M.P., Iannucci G., Giacomotti L., et al. The effect of cladribine on T(1) 'black hole' changes in progressive MS. J Neurol Sci 176 1 (2000) 42-44
258. Giovannoni G., Comi G., Cook S., Rammohan K., Rieckmann P., Soelberg Sørensen P., et al. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N Engl J Med 362 5 (2010) 416-426
259. Polman C.H., Reingold S.C., Edan G., Filippi M., Hartung H.P., Kappos L., et al. Diagnostic criteria for multiple sclerosis: revisions to the "McDonald Criteria". Ann Neurol 58 6 (2005) 840-846
260. Leist T.P., and Vermersch P. The potential role for cladribine in the treatment of multiple sclerosis: clinical experience and development of an oral tablet formulation. Curr Med Res Opin 23 11 (2007) 2667-2676
261. Bruneau J.M., Yea C.M., Spinella-Jeagle S., Fudali C., Woodward K., Robson P.A., et al. Purification of human dihydro-orotate dehydrogenase and its inhibition by A77 1726, the active metabolite of leflunomide. Biochem J 336 Pt 2 (1998) 299-303
262. Nakajima A., Yamanaka H., and Kamatani N. Leflunomide: clinical effectiveness and mechanism of action. Clin Calcium 13 6 (2003) 771-775
263. Korn T., Toyka K., Hartung H.P., and Jung S. Suppression of experimental autoimmune neuritis by leflunomide. Brain 124 Pt 9 (2001) 1791-1802
264. Merrill J.E., Hanak S., Pu S.F., Liang J., Dang C., Iglesias-Bregna D., et al. Teriflunomide reduces behavioral, electrophysiological, and histopathological deficits in the Dark Agouti rat model of experimental autoimmune encephalomyelitis. J Neurol 256 1 (2009) 89-103
265. O'Connor P.W., Li D., Freedman M.S., Bar-Or A., Rice G.P., Confavreux C., et al. A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses. Neurology 66 6 (2006) 894-900
266. Schweckendiek W. Treatment of psoriasis vulgaris. Med Monatsschr 13 2 (1959) 103-104
267. Roll A., Reich K., and Boer A. Use of fumaric acid esters in psoriasis. Indian J Dermatol Venereol Leprol 73 2 (2007) 133-137
268. Mrowietz U., Christophers E., and Altmeyer P. Treatment of psoriasis with fumaric acid esters: results of a prospective multicentre study. German Multicentre Study. Br J Dermatol 138 3 (1998) 456-460
269. Altmeyer P.J., Matthes U., Pawlak F., Hoffmann K., Frosch P.J., Ruppert P., et al. Antipsoriatic effect of fumaric acid derivatives. Results of a multicenter double-blind study in 100 patients. J Am Acad Dermatol 30 6 (1994) 977-981
270. Kolbach D.N., and Nieboer C. Fumaric acid therapy in psoriasis: results and side effects of 2 years of treatment. J Am Acad Dermatol 27 5 Pt 1 (1992) 769-771
271. Moharregh-Khiabani D., Linker R.A., Gold R., and Stangel M. Fumaric acid and its esters: an emerging treatment for multiple sclerosis. Curr Neuropharmacol 7 1 (2009) 60-64
272. Stoof T.J., Flier J., Sampat S., Nieboer C., Tensen C.P., and Boorsma D.M. The antipsoriatic drug dimethylfumarate strongly suppresses chemokine production in human keratinocytes and peripheral blood mononuclear cells. Br J Dermatol 144 6 (2001) 1114-1120
273. Mrowietz U., and Asadullah K. Dimethylfumarate for psoriasis: more than a dietary curiosity. Trends Mol Med 11 1 (2005) 43-48
274. De Jong R., Bezemer A.C., Zomerdijk T.P., van de Pouw-Kraan T., Ottenhoff T.H., and Nibbering P.H. Selective stimulation of T helper 2 cytokine responses by the anti-psoriasis agent monomethylfumarate. Eur J Immunol 26 9 (1996) 2067-2074
275. Treumer F., Zhu K., Gläser R., and Mrowietz U. Dimethylfumarate is a potent inducer of apoptosis in human T cells. J Invest Dermatol 121 6 (2003) 1383-1388
276. Lukashev M., Zeng W., Goetz S., Lee D., Linker R., Gold B., et al. Activation of Nrf2 and modulation of disease progression in EAE models by BG00012 (dimethylfumarate) suggests a novel mechanism of action combining anti-inflammatory and neuroprotective modalities. Mult Scler 13 Suppl. 2 (2007) P503
277. Schilling S., Goelz S., Linker R., Luehder F., and Gold R. Fumaric acid esters are effective in chronic experimental autoimmune encephalomyelitis and suppress macrophagen infiltration. Clin Exp Immunol 145 1 (2006) 101-107
278. Kappos L., Gold R., Miller D.H., Macmanus D.G., Havrdova E., Limmroth V., et al. Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomized, double-blind, placebo-controlled phase IIb study. Lancet 372 9648 (2008) 1463-1472
279. Andersen O., Lycke J., Tollesson P.O., Svenningsson A., Runmarker B., Linde A.S., et al. Linomide reduces the rate of active lesions in relapsing-remitting multiple sclerosis. Neurology 47 4 (1996) 895-900
280. Noseworthy J.H., Wolinsky J.S., Lublin F.D., Whitaker J.N., Linde A., Gjorstrup P., et al. Linomide in relapsing and secondary progressive MS, part I: trial design and clinical results. Neurology 54 9 (2000) 1726-1733
281. Polman C., Barkhof F., Sandberg-Wollheim M., Linde A., Nordle O., and Nederman T. Treatment with laquinimod reduces development of active MRI lesions in relapsing MS. Neurology 64 6 (2005) 987-991
282. Comi G., Pulizzi A., Rovaris M., Abramsky O., Arbizu T., Boiko A., 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 371 9630 (2008) 2085-2092
283. Yong V.W., Wells J., Giuliani F., Casha S., Power C., and Metz L.M. The promise of minocycline in neurology. Lancet Neurol 3 12 (2004) 744-751
284. Metz L.M., Zhang Y., Yeung M., et al. Minocycline reduces gadolinium-enhancing magnetic resonance imaging lesions in multiple sclerosis [letter]. Ann Neurol 55 5 (2004) 756
285. Metz L.M., Li D., Traboulsee A., Myles M.L., Duquette P., Godin J., et al. Glatiramer acetate in combination with minocycline in patients with relapsing-remitting multiple sclerosis: results of a Canadian, multicenter, double-blind, placebo-controlled trial. Mult Scler 15 10 (2009) 1183-1194
286. Youssef S., Stüve O., Patarroyo J.C., Ruiz P.J., Radosevich J.L., Hur E.M., et al. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 420 6911 (2002) 78-84
287. Neuhaus O., Strasser-Fuchs S., Fazekas F., Kieseier B.C., Niederwieser G., Hartung H.P., et al. Statins as immunomodulators: comparison with interferon beta-1b in MS. Neurology 59 7 (2002) 990-997
288. Paul F., Waiczies S., Wuerfel J., Bellmann-Strobl J., Dörr J., Waiczies H., et al. Oral high-dose atorvastatin treatment in relapsing-remitting multiple sclerosis. PLoS ONE 3 4 (2008) e1928
289. Vollmer T., Key L., Durkalski V., Tyor W., Corboy J., Markovic-Plese S., et al. Oral simvastatin treatment in relapsing remitting multiple sclerosis. Lancet 363 9421 (2004) 1607-1608
290. Birnbaum G., Cree B., Altafullah I., Zinser M., and Reder A.T. Combining beta interferon and atorvastatin may increase disease activity in multiple sclerosis. Neurology 71 18 (2008) 1390-1395
291. Hale G., Dyer M.J., Clark M.R., Phillips J.M., Marcus R., Riechmann L., et al. Remission induction in non-Hodgkin Lymphoma with reshaped human monoclonal antibody CAMPATH-1H. Lancet 2 8625 (1988) 1394-1399
292. Crowe J.S., Hall V.S., Smith M.A., Cooper H.J., and Tite J.P. Humanized monoclonal antibody CAMPATH-1H: myeloma cell expression genomic constructs, nucleotide sequence of cDNA constructs and comparison of effector mechanisms of myeloma and Chinese hamster ovary cell-derived material. Clin Exp Immunol 87 1 (1992) 105-110
293. Flynn J.M., and Byrd J.C. Campath-1H monoclonal antibody therapy. Curr Opin Oncol 12 6 (2000) 574-581
294. Cobbold S.P., Hale G., Clarke M.R., and Waldmann H. Purging in auto and allografts: monoclonal antibodies which use human complement and other natural effector mechanisms. Prog Clin Biol Res 333 (1990) 139-151 discussion 152-154
295. Moreau T., Thorpe J., Miller D., Moseley I., Hale G., Waldmann H., et al. Preliminary evidence from magnetic resonance imaging for reduction in disease activity after lymphocyte depletion in multiple sclerosis. Lancet 344 8918 (1994) 298-301
296. Coles A.J., Cox A., Le Page E., Jones J., Trip S.A., Deans J., et al. The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol 253 1 (2006) 98-108
297. Coles A.J., Wing M.G., Molyneux P., Paolillo A., Davie C.M., Hale G., et al. Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis. Ann Neurol 46 3 (1999) 296-304
298. Paolillo A., Coles A.J., Molyneux P.D., Gawne-Cain M., MacManus D., Barker G.J., et al. Quantitative MRI in patients with secondary progressive MS treated with monoclonal antibody Campath 1H. Neurology 53 4 (1999) 751-757
299. Coles A.J., Compston D.A., Lake S.L., Moran S., Margolin D.H., et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med 359 17 (2008) 1786-1801
300. Grillo-López A.J. Rituximab: an insider's historical perspective. Semin Oncol 27 Suppl. 12 (2000) 9-16
301. Maloney D.G., Grillo-López A.J., White C.A., Bodkin D., Schilder R.J., Neidhart J.A., et al. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low grade non-Hodgkin's lymphoma. Blood 90 6 (1997) 2188-2195
302. Fanale M.A., and Younes A. Monoclonal antibodies in the treatment of non-Hodgkin's lymphoma. Drugs 67 3 (2007) 333-350
303. Cohen S.B., Emery P., Greenwald M.W., Dougados M., Furie R.A., Genovese M.C., et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum 54 9 (2006) 2793-2806
304. Lucchinetti C., Bruck W., Parisi J., Scheithauer B., Rodriguez M., and Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 47 6 (2000) 707-717
305. Esiri M.M. Immunoglobulin-containing cells in multiple-sclerosis plaques. Lancet 2 8036 (1977) 478
306. Genain C.P., Cannella B., Hauser S.L., and Raine C.S. Identification of autoantibodies associated with myelin damage in multiple sclerosis. Nat Med 5 2 (1999) 170-175
307. Villar L.M., Masjuan J., González-Porqué P., Plaza J., Sádaba M.C., Roldán E., et al. Intrathecal IgM synthesis in neurologic diseases: relationship with disability in MS. Neurology 58 5 (2002) 824-826
308. Qin Y., Duquette P., Zhang Y., Olek M., Da R.R., Richardson J., et al. Intrathecal B-cell clonal expansion, an early sign of humoral immunity, in the cerebrospinal fluid of patients with clinically isolated syndrome suggestive of multiple sclerosis. Lab Invest 83 7 (2003) 1081-1088
309. Corcione A., Casazza S., Ferretti E., Giunti D., Zappia E., Pistorio A., et al. Recapitulation of B cell differentiation in the central nervous system of patients with multiple sclerosis. Proc Natl Acad Sci USA 101 30 (2004) 11064-11069
310. Serafini B., Rosicarelli B., Magliozzi R., Stigliano E., and Aloisi F. Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol 14 2 (2004) 164-174
311. Prineas J.W., and Wright R.G. Macrophages, lymphocytes, and plasma cells in the perivascular compartment in chronic multiple sclerosis. Lab Invest 38 4 (1978) 409-421
312. Sellebjerg F., Jensen J., and Ryder L.P. Costimulatory CD80 (B7-1) and CD86 (B7-2) on cerebrospinal fluid cells in multiple sclerosis. J Neuroimmunol 84 2 (1998) 179-187
313. McFarland H.F. The B cell: old player, new position on the team [editorial]. N Engl J Med 358 7 (2008) 664-665
314. Dalakas M.C. Inhibition of B cell functions: implications for neurology. Neurology 70 23 (2008) 2252-2260
315. Monson N.L., Cravens P.D., Frohman E.M., Hawker K., and Racke M.K. Effect of rituximab on the peripheral blood and cerebrospinal fluid B cells in patients with primary progressive multiple sclerosis. Arch Neurol 62 2 (2005) 258-264
316. Cross A.H., Stark J.L., Lauber J., Ramsbottom M.J., and Lyons J.A. Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients. J Neuroimmunol 180 1/2 (2006) 63-70
317. Hauser S.L., Waubant E., Arnold D.L., Vollmer T., Antel J., Fox R.J., et al. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 358 7 (2008) 676-688
318. Calabrese L.H., Molloy E.S., Huang D., and Ransohoff R.M. Progressive multifocal leukoencephalopathy in rheumatic diseases: evolving clinical and pathologic patterns of disease. Arthritis Rheum 56 7 (2007) 2116-2128
319. Boren E.J., Cheema G.S., Naguwa S.M., Ansari A.A., and Gershwin M.E. The emergence of progressive multifocal leukoencephalopathy (PML) in rheumatic diseases. J Autoimmun 30 1/2 (2008) 90-98
320. Freim Wahl S.G., Folvik M.R., and Torp S.H. Progressive multifocal leukoencephalopathy in a lymphoma patient with complete remission after treatment with cytostatics and rituximab: case report and review of the literature. Clin Neuropathol 26 2 (2007) 68-73
321. Martin R. Humanized anti-CD25 antibody treatment with daclizumab in multiple sclerosis. Neurodegener Dis 5 1 (2008) 23-26
322. Bielekova B., Catalfamo M., Reichert-Scrivner S., Packer A., Cerna M., Waldmann T.A., 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 103 15 (2006) 5941-5946
323. Oh U., Blevins G., Griffith C., Richert N., Maric D., Lee C.R., et al. Regulatory T cells are reduced during anti-CD25 antibody treatment of multiple sclerosis. Arch Neurol 66 4 (2009) 471-479
324. Kaufman M.D., Wynn D.R., and Montalban X. A phase 2 randomized, double-blinded, placebo-controlled, multicenter study of subcutaneous daclizumab, a humanized, anti-CD-25 monoclonal antibody, in patients with active, relapsing forms of multiple sclerosis: week 44 results [abstract PL01.003]. Neurology 70 Suppl. 1 (2008) A220
325. Rose J.W., Watt H.E., White A.T., and Carlson N.G. Treatment of multiple sclerosis with an anti-interleukin-2 receptor monoclonal antibody. Ann Neurol 56 6 (2004) 864-867
326. Bielekova B., Richert N., Howard T., Blevins G., Markovic-Plese S., McCartin J., et al. Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon. Proc Natl Acad Sci USA 101 23 (2004) 8705-8708
327. Rose J.W., Burns J.B., Bjorklund J., Klein J., Watt H.E., and Carlson N.G. Daclizumab phase II trial in relapsing and remitting multiple sclerosis: MRI and clinical results. Neurology 69 8 (2007) 785-789
328. Trojano M., Pellegrini F., Fuiani A., Paolicelli D., Zipoli V., Zimatore G.B., et al. New natural history of interferon-beta-treated relapsing multiple sclerosis. Ann Neurol 61 4 (2007) 300-306