Treatment of multiple sclerosis: Current concepts and future perspectives

Journal of Neurology

Volumn 258, Issue 10, 2011, Pages 1747-1762

  Buck, Dorothea ^a   Hemmer, Bernhard ^a  

^a TECHNICAL UNIVERSITY OF MUNICH   (Germany)

Author keywords

Clinical trials; Immunotherapy; Multiple sclerosis; Treatment

Indexed keywords

ALEMTUZUMAB; ANTIVIRUS AGENT; AZATHIOPRINE; BETA INTERFERON; BETA1A INTERFERON; BG 00012; CAMPATH 1 H; CHLOROQUINE; CLADRIBINE; CORTICOSTEROID; CYCLOSPORIN A; DACLIZUMAB; DANAZOL; FINGOLIMOD; FIRATEGRAST; FUMARIC ACID DIMETHYL ESTER; GADOLINIUM; GLATIRAMER; INTERFERON BETA SERINE; LAQUINIMOD; LEFLUNOMIDE; METHOTREXATE; METHYLPREDNISOLONE; MITOXANTRONE; MOVECTRO; NATALIZUMAB; OCRELIZUMAB; OFATUMUMAB; RALENOVA; RITUXIMAB; ROQUINIMEX; TERIFLUNOMIDE; UNCLASSIFIED DRUG;

ABDOMINAL PAIN; ADD ON THERAPY; ALLERGIC ENCEPHALOMYELITIS; ALOPECIA; AMENORRHEA; ANTIVIRAL THERAPY; ARTHRALGIA; ATRIOVENTRICULAR BLOCK; BRADYCARDIA; COMPARATIVE EFFECTIVENESS; CORTICOSTEROID THERAPY; DIARRHEA; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG ERUPTION; DRUG FEVER; DRUG HYPERSENSITIVITY; DRUG INDUCED HEADACHE; DRUG MEGADOSE; DRUG PENETRATION; DRUG SAFETY; DRUG SYNTHESIS; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPEPSIA; FATIGUE; FEMALE INFERTILITY; FLUSHING; HEART INFARCTION; HERPES SIMPLEX; HERPES ZOSTER; HUMAN; HYPERTENSION; IMMUNOMODULATION; IMMUNOSUPPRESSIVE TREATMENT; INFECTION; INFESTATION; INFLAMMATION; INJECTION SITE LIPODYSTROPHY; INJECTION SITE REACTION; KIDNEY GRAFT REJECTION; LIPODYSTROPHY; LIVER TOXICITY; LOADING DRUG DOSE; LOW DRUG DOSE; LYMPHADENOPATHY; LYMPHOCYTOPENIA; LYMPHOCYTOSIS; MALE INFERTILITY; MONOTHERAPY; MOUTH ULCER; MULTIPLE SCLEROSIS; NAUSEA; NAUSEA AND VOMITING; NEOPLASM; NEUTROPENIA; NONHUMAN; OPPORTUNISTIC INFECTION; PANCYTOPENIA; PERICARDITIS; PRIORITY JOURNAL; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; PSORIASIS; RELAPSE; RESPIRATORY TRACT INFECTION; RETINA MACULA EDEMA; REVIEW; RHEUMATOID ARTHRITIS; SIDE EFFECT; SYSTEMIC DISEASE; SYSTEMIC INFLAMMATORY RESPONSE SYNDROME; TERATOGENICITY; THROMBOCYTOPENIA; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION; UTERUS MYOMA; VIRUS REACTIVATION; VOMITING; WEIGHT REDUCTION;

CLINICAL TRIALS AS TOPIC; HUMANS; IMMUNOSUPPRESSIVE AGENTS; IMMUNOTHERAPY; MULTIPLE SCLEROSIS;

EID: 80054757199     PISSN: 03405354     EISSN: 14321459     Source Type: Journal    
DOI: 10.1007/s00415-011-6101-2     Document Type: Review

References (116)

1. M Sospedra R Martin 2005 Immunology of multiple sclerosis Annu Rev Immunol 23 683 747 15771584 1:CAS:528:DC%2BD2MXktFOju7w%3D 10.1146/annurev. immunol.23.021704.115707 (Pubitemid 40563183)
2. B Hemmer S Nessler D Zhou B Kieseier HP Hartung 2006 Immunopathogenesis and immunotherapy of multiple sclerosis Nat Clin Pract Neurol 2 201 211 16932551 1:CAS:528:DC%2BD28XktlyqsLk%3D 10.1038/ncpneuro0154
3. RP Kinkel C Kollman P O'Connor TJ Murray J Simon, et al. 2006 IM interferon beta-1a delays definite multiple sclerosis 5 years after a first demyelinating event Neurology 66 678 684 16436649 10.1212/01.wnl.0000200778. 65597.ae 1:CAS:528:DC%2BD28Xhs1Grtb8%3D (Pubitemid 43739821)
4. L Kappos MS Freedman CH Polman G Edan HP Hartung, et al. 2007 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 370 389 397 17679016 1:CAS:528:DC%2BD2sXosFKktLc%3D 10.1016/S0140-6736(07)61194-5 (Pubitemid 47189673)
5. G Comi M Filippi JS Wolinsky 2001 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 49 290 297 11261502 1:CAS:528:DC%2BD3MXisVyqtL0%3D 10.1002/ana.64 (Pubitemid 32202781)
6. T Kuhlmann G Lingfeld A Bitsch J Schuchardt W Bruck 2002 Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time Brain 125 2202 2212 12244078 10.1093/brain/awf235
7. Lukas C, Minneboo A, de Groot V, Moraal B, Knol DL, et al (2010) Early central atrophy rate predicts 5 year clinical outcome in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2010/09/10 edn pp 1351-1356
8. DW Paty DK Li 1993 Interferon beta-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 43 662 667 8469319 1:STN:280: DyaK3s3is1Sqtw%3D%3D (Pubitemid 23121952)
9. Ebers GC, PRISMS (Prevention of Relapses and Disability by Interferon β-1a Subcutaneously in Multiple Sclerosis) Study Group (1998) Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. Lancet 352:1498-1504 (Pubitemid 28512925)
10. LD Jacobs DL Cookfair RA Rudick RM Herndon JR Richert, et al. 1996 Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG) Ann Neurol 39 285 294 8602746 1:CAS:528:DyaK28XisFyrsLY%3D 10.1002/ana.410390304 (Pubitemid 26100751)
11. O Stuve JL Bennett B Hemmer H Wiendl MK Racke, et al. 2008 Pharmacological treatment of early multiple sclerosis Drugs 68 73 83 18081373 1:CAS:528:DC%2BD1cXisVOhurg%3D 10.2165/00003495-200868010-00005 (Pubitemid 350275685)
12. The IFNB Multiple Sclerosis Study Group (1993) Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 43:655-661
13. L Kappos CH Polman MS Freedman G Edan HP Hartung, et al. 2006 Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes Neurology 67 1242 1249 16914693 1:CAS:528:DC%2BD28XhtFyqtLfL 10.1212/01.wnl.0000237641.33768.8d (Pubitemid 44563835)
14. LD Jacobs RW Beck JH Simon RP Kinkel CM Brownscheidle, et al. 2000 Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group N Engl J Med 343 898 904 11006365 1:CAS:528:DC%2BD3cXntFOkt7k%3D 10.1056/NEJM200009283431301
15. AT Reder GC Ebers A Traboulsee D Li D Langdon, et al. 2010 Cross-sectional study assessing long-term safety of interferon-beta-1b for relapsing-remitting MS Neurology 74 1877 1885 20530324 1:CAS:528: DC%2BC3cXntF2gtb8%3D 10.1212/WNL.0b013e3181e240d0
16. Foulds B, Richman S, Glick G, Onigman T, Hyde R (2010) Pregnancy outcomes from the Avonex (interferon beta-1a) Pregnancy Exposure Registry. Mult Scler vol 16 Suppl 10, Poster 894 at ECTRIMS 2010
17. H Schellekens 2002 Immunogenicity of therapeutic proteins: clinical implications and future prospects Clin Ther 24 1720 1740 12501870 1:CAS:528:DC%2BD38Xpslekurw%3D 10.1016/S0149-2918(02)80075-3 (discussion 1719) (Pubitemid 35440946)
18. F Sellebjerg M Krakauer D Hesse LP Ryder I Alsing, et al. 2009 Identification of new sensitive biomarkers for the in vivo response to interferon-beta treatment in multiple sclerosis using DNA-array evaluation Eur J Neurol 16 1291 1298 19558503 1:STN:280:DC%2BD1MjntFKltw%3D%3D 10.1111/j.1468-1331.2009.02716.x
19. D Hesse F Sellebjerg PS Sorensen 2009 Absence of MxA induction by interferon beta in patients with MS reflects complete loss of bioactivity Neurology 73 372 377 19652141 1:CAS:528:DC%2BD1MXptVGksbc%3D 10.1212/WNL.0b013e3181b04c98
20. AR Pachner JD Warth A Pace S Goelz 2009 Effect of neutralizing antibodies on biomarker responses to interferon beta: the INSIGHT study Neurology 73 1493 1500 19884577 1:CAS:528:DC%2BD1MXhtlCmsrjK 10.1212/WNL.0b013e3181bf98db
21. CH Polman A Bertolotto F Deisenhammer G Giovannoni HP Hartung, et al. 2010 Recommendations for clinical use of data on neutralising antibodies to interferon-beta therapy in multiple sclerosis Lancet Neurol 9 740 750 20610349 1:CAS:528:DC%2BC3cXpsFajur0%3D 10.1016/S1474-4422(10)70103-4
22. F Deisenhammer 2009 Neutralizing antibodies to interferon-beta and other immunological treatments for multiple sclerosis: prevalence and impact on outcomes CNS Drugs 23 379 396 19453200 1:CAS:528:DC%2BD1MXosVeiu78%3D 10.2165/00023210-200923050-00003
23. A Bertolotto S Malucchi E Milano A Castello M Capobianco, et al. 2000 Interferon beta neutralizing antibodies in multiple sclerosis: neutralizing activity and cross-reactivity with three different preparations Immunopharmacology 48 95 100 10936507 1:CAS:528:DC%2BD3cXlsFequ7s%3D 10.1016/S0162-3109(00)00182-X (Pubitemid 30608666)
24. PS Sorensen N Koch-Henriksen C Ross KM Clemmesen K Bendtzen 2005 Appearance and disappearance of neutralizing antibodies during interferon-beta therapy Neurology 65 33 39 15888603 1:CAS:528:DC%2BD2MXlsFajsrs%3D 10.1212/01.WNL.0000166049.51502.6A (Pubitemid 40967773)
25. B Petersen K Bendtzen N Koch-Henriksen M Ravnborg C Ross, et al. 2006 Persistence of neutralizing antibodies after discontinuation of IFNbeta therapy in patients with relapsing-remitting multiple sclerosis Mult Scler 12 247 252 16764336 10.1191/135248505ms1324oa (Pubitemid 43832494)
26. van der Voort LF, Gilli F, Bertolotto A, Knol DL, Uitdehaag BM, et al Clinical effect of neutralizing antibodies to interferon beta that persist long after cessation of therapy for multiple sclerosis. Arch Neurol 67:402-407
27. S Hoffmann S Cepok V Grummel K Lehmann-Horn J Hackermuller, et al. 2008 HLA-DRB1*0401 and HLA-DRB1*0408 are strongly associated with the development of antibodies against interferon-beta therapy in multiple sclerosis Am J Hum Genet 83 219 227 18656179 1:CAS:528:DC%2BD1cXpvVOhs7s%3D 10.1016/j.ajhg.2008.07.006
28. Buck D, Cepok S, Hoffmann S, Grummel V, Jochim A, Berthele A, Hartung HP, Wassmuth R, Hemmer B (2011) Influence of the HLA-DRB1 Genotype on antibody development to Interferon Beta in Multiple Sclerosis. Arch Neurol 68:480-487
29. H Panitch DS Goodin G Francis P Chang PK Coyle, et al. 2002 Randomized, comparative study of interferon beta-1a treatment regimens in MS: the EVIDENCE Trial Neurology 59 1496 1506 12451188 1:CAS:528:DC%2BD38XosVCmtro%3D (Pubitemid 35387053)
30. L Durelli E Verdun P Barbero M Bergui E Versino, et al. 2002 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 1453 1460 11988242 1:CAS:528:DC%2BD38Xjt1SktrY%3D 10.1016/S0140-6736(02)08430-1 (Pubitemid 34457761)
31. DP Baker RB Pepinsky M Brickelmaier RS Gronke X Hu, et al. 2010 PEGylated interferon beta-1a: meeting an unmet medical need in the treatment of relapsing multiple sclerosis J Interferon Cytokine Res 30 777 785 20836711 1:CAS:528:DC%2BC3cXht1WmtbfF 10.1089/jir.2010.0092
32. R Arnon R Aharoni 2004 Mechanism of action of glatiramer acetate in multiple sclerosis and its potential for the development of new applications Proc Natl Acad Sci USA 101 Suppl 2 14593 14598 15371592 1:CAS:528: DC%2BD2cXovVeqsrY%3D 10.1073/pnas.0404887101 (Pubitemid 39346729)
33. MS Weber T Prod'homme S Youssef SE Dunn CD Rundle, et al. 2007 Type II monocytes modulate T cell-mediated central nervous system autoimmune disease Nat Med 13 935 943 17676050 1:CAS:528:DC%2BD2sXos1Cjsbc%3D 10.1038/nm1620 (Pubitemid 47222047)
34. KP Johnson BR Brooks JA Cohen CC Ford J Goldstein, et al. 1995 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 45 1268 1276 7617181 1:STN:280:DyaK2Mzkt1eqtQ%3D%3D
35. G Comi V Martinelli M Rodegher L Moiola O Bajenaru, et al. 2009 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 1503 1511 19815268 1:CAS:528:DC%2BD1MXhtlCmt7zN 10.1016/S0140-6736(09)61259-9
36. C Ford AD Goodman K Johnson N Kachuck JW Lindsey, et al. 2010 Continuous long-term immunomodulatory therapy in relapsing multiple sclerosis: results from the 15-year analysis of the US prospective open-label study of glatiramer acetate Mult Scler 16 342 350 20106943 1:CAS:528:DC%2BC3cXlt1Olt7w%3D 10.1177/1352458509358088
37. P O'Connor M Filippi B Arnason G Comi S Cook, et al. 2009 250 microg or 500 microg interferon beta-1b versus 20 mg glatiramer acetate in relapsing-remitting multiple sclerosis: a prospective, randomised, multicentre study Lancet Neurol 8 889 897 19729344 10.1016/S1474-4422(09)70226-1 1:CAS:528:DC%2BD1MXht1Kitr7O
38. DD Mikol F Barkhof P Chang PK Coyle DR Jeffery, et al. 2008 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 7 903 914 18789766 1:CAS:528:DC%2BD1cXht1enu7%2FN 10.1016/S1474-4422(08)70200-X
39. CH Polman PW O'Connor E Havrdova M Hutchinson L Kappos, et al. 2006 A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis N Engl J Med 354 899 910 16510744 1:CAS:528:DC%2BD28XitVertL4%3D 10.1056/NEJMoa044397
40. RA Rudick WH Stuart PA Calabresi C Confavreux SL Galetta, et al. 2006 Natalizumab plus interferon beta-1a for relapsing multiple sclerosis N Engl J Med 354 911 923 16510745 1:CAS:528:DC%2BD28XitVertLw%3D 10.1056/NEJMoa044396
41. EO Major 2010 Progressive multifocal leukoencephalopathy in patients on immunomodulatory therapies Annu Rev Med 61 35 47 19719397 1:CAS:528: DC%2BC3cXisFyls7g%3D 10.1146/annurev.med.080708.082655
42. L Gorelik M Lerner S Bixler M Crossman B Schlain, et al. 2010 Anti-JC virus antibodies: implications for PML risk stratification Ann Neurol 68 295 303 20737510 10.1002/ana.22128
43. MC Monaco WJ Atwood M Gravell CS Tornatore EO Major 1996 JC virus infection of hematopoietic progenitor cells, primary B lymphocytes, and tonsillar stromal cells: implications for viral latency J Virol 70 7004 7012 8794345 1:CAS:528:DyaK28XlslWjs7w%3D (Pubitemid 26307415)
44. P Ferrante R Caldarelli-Stefano E Omodeo-Zorini L Vago R Boldorini, et al. 1995 PCR detection of JC virus DNA in brain tissue from patients with and without progressive multifocal leukoencephalopathy J Med Virol 47 219 225 8551272 1:CAS:528:DyaK28Xjsl2l 10.1002/jmv.1890470306
45. O Stuve CM Marra KR Jerome L Cook PD Cravens, et al. 2006 Immune surveillance in multiple sclerosis patients treated with natalizumab Ann Neurol 59 743 747 16634029 1:CAS:528:DC%2BD28XkvFKhsLk%3D 10.1002/ana.20858 (Pubitemid 43673151)
46. Y Chen E Bord T Tompkins J Miller CS Tan, et al. 2009 Asymptomatic reactivation of JC virus in patients treated with natalizumab N Engl J Med 361 1067 1074 19741227 1:CAS:528:DC%2BD1MXhtFartr%2FF 10.1056/NEJMoa0904267
47. S Jilek E Jaquiery HH Hirsch A Lysandropoulos M Canales, et al. 2010 Immune responses to JC virus in patients with multiple sclerosis treated with natalizumab: a cross-sectional and longitudinal study Lancet Neurol 9 264 272 20117055 1:CAS:528:DC%2BC3cXjs12lur0%3D 10.1016/S1474-4422(10)70006-5
48. RA Rudick PW O'Connor CH Polman AD Goodman SS Ray, et al. 2010 Assessment of JC virus DNA in blood and urine from natalizumab-treated patients Ann Neurol 68 304 310 20737514 10.1002/ana.22107
49. Miller D, Weber T, Montalban X, Grove R, Dua P, Wardell C, Graff O (2010) Phase II trial of firategrast shows that oral anti-alpha4 therapy can suppress new MRI lesions in relapsing-remitting multiple sclerosis. Multiple sclerosis, abstract at ECTRIMS 2010 (Data on file)
50. JJ Marriott JM Miyasaki G Gronseth PW O'Connor 2010 Evidence report: the efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 74 1463 1470 20439849 1:CAS:528:DC%2BC3cXls1Cktb4%3D 10.1212/WNL.0b013e3181dc1ae0
51. HP Hartung R Gonsette N Konig H Kwiecinski A Guseo, et al. 2002 Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial Lancet 360 2018 2025 12504397 10.1016/S0140-6736(02)12023-X (Pubitemid 36026580)
52. Martinelli Boneschi F, Rovaris M, Capra R, Comi G (2005) Mitoxantrone for multiple sclerosis. Cochrane Database Syst Rev:CD002127
53. M Matloubian CG Lo G Cinamon MJ Lesneski Y Xu, et al. 2004 Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1 Nature 427 355 360 14737169 1:CAS:528:DC%2BD2cXltFCguw%3D%3D 10.1038/nature02284 (Pubitemid 38133663)
54. V Brinkmann A Billich T Baumruker P Heining R Schmouder, et al. 2010 Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis Nat Rev Drug Discov 9 883 897 21031003 1:CAS:528:DC%2BC3cXhtlCqsr%2FL 10.1038/nrd3248
55. CA Foster LM Howard A Schweitzer E Persohn PC Hiestand, et al. 2007 Brain penetration of the oral immunomodulatory drug FTY720 and its phosphorylation in the central nervous system during experimental autoimmune encephalomyelitis: consequences for mode of action in multiple sclerosis J Pharmacol Exp Ther 323 469 475 17682127 1:CAS:528:DC%2BD2sXht1ynsLfP 10.1124/jpet.107.127183 (Pubitemid 350005125)
56. Kowarik MC, Pellkofer HL, Cepok S, Korn T, Kümpfel T, Buck D, Hohlfeld R, Berthele A, Hemmer B (2011) Differential effects of fingolimod (FTY720) therapy on immune cells in the cerebrospinal fluid and blood of multiple sclerosis patients. Neurology 76:1214-1221
57. L Kappos EW Radue P O'Connor C Polman R Hohlfeld, et al. 2010 A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis N Engl J Med 362 387 401 20089952 1:CAS:528:DC%2BC3cXhvVWltr4%3D 10.1056/NEJMoa0909494
58. JA Cohen F Barkhof G Comi HP Hartung BO Khatri, et al. 2010 Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis N Engl J Med 362 402 415 20089954 1:CAS:528:DC%2BC3cXhvVWrsbk%3D 10.1056/NEJMoa0907839
59. Schmouder R, Aradhye S, O′Connor P, Kappos L (2006) Pharmacodynamic effects of oral fingolimod (FTY720). Poster at ECTRIMS
60. A Schwarz M Korporal W Hosch R Max B Wildemann 2010 Critical vasospasm during fingolimod (FTY720) treatment in a patient with multiple sclerosis Neurology 74 2022 2024 20548047 1:STN:280:DC%2BC3crgtlynsw%3D%3D 10.1212/WNL.0b013e3181e3972b
61. F Leypoldt A Munchau F Moeller M Bester C Gerloff, et al. 2009 Hemorrhaging focal encephalitis under fingolimod (FTY720) treatment: a case report Neurology 72 1022 1024 19289744 1:STN:280:DC%2BD1M3ht1ansA%3D%3D 10.1212/01.wnl.0000344567.51394.e3
62. E Beutler 1992 Cladribine (2-chlorodeoxyadenosine) Lancet 340 952 956 1357355 1:STN:280:DyaK3s%2FitlaktA%3D%3D 10.1016/0140-6736(92)92826-2
63. J Liliemark 1997 The clinical pharmacokinetics of cladribine Clin Pharmacokinet 32 120 131 9068927 1:CAS:528:DyaK2sXitVWqsb8%3D 10.2165/00003088-199732020-00003 (Pubitemid 27104411)
64. E Beutler 1994 New chemotherapeutic agent: 2-chlorodeoxyadenosine Semin Hematol 31 40 45 7907189 1:STN:280:DyaK2c7mslKisQ%3D%3D (Pubitemid 24031130)
65. JS Romine JC Sipe JA Koziol J Zyroff E Beutler 1999 A double-blind, placebo-controlled, randomized trial of cladribine in relapsing-remitting multiple sclerosis Proc Assoc Am Physicians 111 35 44 9893155 1:CAS:528:DyaK1MXms1OrsQ%3D%3D 10.1046/j.1525-1381.1999.09115.x (Pubitemid 29047108)
66. G Giovannoni G Comi S Cook K Rammohan P Rieckmann, et al. 2010 A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis N Engl J Med 362 416 426 20089960 1:CAS:528:DC%2BC3cXhvVaitr0%3D 10.1056/NEJMoa0902533
67. RR Bartlett M Dimitrijevic T Mattar T Zielinski T Germann, et al. 1991 Leflunomide (HWA 486), a novel immunomodulating compound for the treatment of autoimmune disorders and reactions leading to transplantation rejection Agents Actions 32 10 21 2058454 1:CAS:528:DyaK3MXit1Squr8%3D 10.1007/BF01983301
68. N Alcorn S Saunders R Madhok 2009 Benefit-risk assessment of leflunomide: an appraisal of leflunomide in rheumatoid arthritis 10 years after licensing Drug Saf 32 1123 1134 19916579 1:CAS:528:DC%2BC3cXltVCntQ%3D%3D 10.2165/11316650-000000000-00000
69. RA Williamson CM Yea PA Robson AP Curnock S Gadher, et al. 1995 Dihydroorotate dehydrogenase is a high affinity binding protein for A77 1726 and mediator of a range of biological effects of the immunomodulatory compound J Biol Chem 270 22467 22472 7673235 1:CAS:528:DyaK2MXot1Ght7c%3D 10.1074/jbc.270.38.22467
70. Claussen MC, Korn T (2011) Immune mechanisms of new therapeutic strategies in MS - Teriflunomide. Clin Immunol (in press)
71. RT Elder X Xu JW Williams H Gong A Finnegan, et al. 1997 The immunosuppressive metabolite of leflunomide, A77 1726, affects murine T cells through two biochemical mechanisms J Immunol 159 22 27 9200434 1:CAS:528:DyaK2sXktFChur0%3D (Pubitemid 127493680)
72. LC Hamilton I Vojnovic TD Warner 1999 A771726, the active metabolite of leflunomide, directly inhibits the activity of cyclo-oxygenase-2 in vitro and in vivo in a substrate-sensitive manner Br J Pharmacol 127 1589 1596 10455314 1:CAS:528:DyaK1MXlt1ChtLc%3D 10.1038/sj.bjp.0702708 (Pubitemid 29368992)
73. O'Connor P, Wolinsky J, Confavreux C, Comi G, Kappos L, Olsson TP, Benzerdjeb H, Wamil B, Wang L, Miller A and Freedman MS (2010) A placebo-controlled phase III trial (TEMSO) of oral teriflunomide in relapsing multiple sclerosis: clinical efficacy and safety outcomes. Multiple Sclerosis, Abstract at ECTRIMS 2010 (Data on file)
74. Wolinsky J, O'Connor P, Confavreux C, Comi G, Kappos L, Olsson T, Truffinet P, Wang L, Miller A and Freedman MS (2010) A placebo-controlled phase III trial (TEMSO) of oral teriflunomide in relapsing multiple sclerosis: magnetic resonance imaging (MRI) outcomes. Multiple Sclerosis, Abstract at ECTRIMS 2010 (Data on file)
75. S Suissa M Hudson P Ernst 2006 Leflunomide use and the risk of interstitial lung disease in rheumatoid arthritis Arthritis Rheum 54 1435 1439 16645972 1:CAS:528:DC%2BD28XlsFSqu74%3D 10.1002/art.21806
76. K Warnatz HH Peter M Schumacher L Wiese A Prasse, et al. 2003 Infectious CNS disease as a differential diagnosis in systemic rheumatic diseases: three case reports and a review of the literature Ann Rheum Dis 62 50 57 12480669 1:STN:280:DC%2BD38jjvFyqsQ%3D%3D 10.1136/ard.62.1.50 (Pubitemid 36005795)
77. CD Chambers DL Johnson LK Robinson SR Braddock R Xu, et al. 2010 Birth outcomes in women who have taken leflunomide during pregnancy Arthritis Rheum 62 1494 1503 20131283
78. M Freedman WJ Byrnes C Confavreux G Comi G Frangin L Kappos T Olsson A Miller PW O'Connor 2009 Oral teriflunomide or placebo added to interferon beta for 6 months in patients with relapsing multiple sclerosis: safety and efficacy results Mult Scl 15 S273
79. M Freedman G Frangin C Confavreux G Comi WJ Byrnes L Kappos T Olsson A Miller PW O'Connor 2010 Oral teriflunomide or placebo added to glatiramer acetate for 6 months in patients with relapsing multiple sclerosis: safety and efficacy results Neurology 74 A293
80. IL Tan GJ Lycklama a Nijeholt CH Polman HJ Ader F Barkhof 2000 Linomide in the treatment of multiple sclerosis: MRI results from prematurely terminated phase-III trials Mult Scler 6 99 104 10773855 (Pubitemid 30218903)
81. C Polman F Barkhof M Sandberg-Wollheim A Linde O Nordle, et al. 2005 Treatment with laquinimod reduces development of active MRI lesions in relapsing MS Neurology 64 987 991 15781813 1:CAS:528:DC%2BD2MXhvVShs7c%3D 10.1212/01.WNL.0000154520.48391.69 (Pubitemid 40388448)
82. A Tselis 2010 Laquinimod, a new oral autoimmune modulator for the treatment of relapsing-remitting multiple sclerosis Curr Opin Investig Drugs 11 577 585 20419604 1:CAS:528:DC%2BC3cXnt1KgsLc%3D
83. G Comi A Pulizzi M Rovaris O Abramsky T Arbizu, et al. 2008 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 2085 2092 18572078 1:STN:280:DC%2BD1cvgsVegtQ%3D%3D 10.1016/S0140-6736(08)60918-6 (Pubitemid 351842581)
84. G Comi O Abramsky T Arbizu A Boyko R Gold, et al. 2010 Oral laquinimod in patients with relapsing-remitting multiple sclerosis: 36-week double-blind active extension of the multi-centre, randomized, double-blind, parallel-group placebo-controlled study Mult Scler 16 1360 1366 20834039 1:STN:280: DC%2BC3cblvVygtQ%3D%3D 10.1177/1352458510378127
85. K Reich D Thaci U Mrowietz A Kamps M Neureither, et al. 2009 Efficacy and safety of fumaric acid esters in the long-term treatment of psoriasis-a retrospective study (FUTURE) J Dtsch Dermatol Ges 7 603 611 19459898
86. D Moharregh-Khiabani RA Linker R Gold M Stangel 2009 Fumaric acid and its esters: an emerging treatment for multiple sclerosis Curr Neuropharmacol 7 60 64 19721818 1:CAS:528:DC%2BD1MXhtVWqsrfM 10.2174/157015909787602788
87. L Kappos R Gold DH Miller DG Macmanus E Havrdova, et al. 2008 Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study Lancet 372 1463 1472 18970976 1:CAS:528:DC%2BD1cXht12gtLrE 10.1016/S0140-6736(08)61619-0
88. TA Waldmann 2007 Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey J Clin Immunol 27 1 18 17216565 1:CAS:528: DC%2BD2sXhsVyqu7c%3D 10.1007/s10875-006-9060-0 (Pubitemid 46224930)
89. R Martin 2008 Humanized anti-CD25 antibody treatment with daclizumab in multiple sclerosis Neurodegener Dis 5 23 26 18075271 1:CAS:528: DC%2BD2sXhsVanur3I 10.1159/000109934 (Pubitemid 350261812)
90. D Wynn M Kaufman X Montalban T Vollmer J Simon, et al. 2010 Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta Lancet Neurol 9 381 390 20163990 1:CAS:528:DC%2BC3cXltF2ktL4%3D 10.1016/S1474-4422(10) 70033-8
91. B Bielekova N Richert T Howard G Blevins S Markovic-Plese, et al. 2004 Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon beta Proc Natl Acad Sci USA 101 8705 8708 15161974 1:CAS:528:DC%2BD2cXltFKksb8%3D 10.1073/pnas.0402653101 (Pubitemid 38745835)
92. MA Rojas NG Carlson TL Miller JW Rose 2009 Long-term daclizumab therapy in relapsing-remitting multiple sclerosis Ther Adv Neurol Disord 2 291 297 21180619 10.1177/1756285609337992
93. EN Ali BC Healy LA Stazzone BA Brown HL Weiner, et al. 2009 Daclizumab in treatment of multiple sclerosis patients Mult Scler 15 272 274 19136546 1:STN:280:DC%2BD1M3gtlCrtA%3D%3D 10.1177/1352458508097468
94. B Bielekova T Howard AN Packer N Richert G Blevins, et al. 2009 Effect of anti-CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis Arch Neurol 66 483 489 19364933 10.1001/archneurol.2009.50
95. JL Jones AJ Coles 2008 Campath-1H treatment of multiple sclerosis Neurodegener Dis 5 27 31 18075272 1:CAS:528:DC%2BD2sXhsVanur3K 10.1159/000109935 (Pubitemid 350261813)
96. MH Gilleece TM Dexter 1993 Effect of Campath-1H antibody on human hematopoietic progenitors in vitro Blood 82 807 812 7687895 1:CAS:528: DyaK3sXmtVWnsb0%3D (Pubitemid 23221659)
97. AJ Coles A Cox E Le Page J Jones SA Trip, et al. 2006 The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy J Neurol 253 98 108 16044212 10.1007/s00415-005-0934-5 (Pubitemid 43157395)
98. JL Jones CL Phuah AL Cox SA Thompson M Ban, et al. 2009 IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H) J Clin Invest 119 2052 2061 19546505 1:CAS:528:DC%2BD1MXosVCrs7s%3D
99. A Coles J Deans A Compston 2004 Campath-1H treatment of multiple sclerosis: lessons from the bedside for the bench Clin Neurol Neurosurg 106 270 274 15177782 10.1016/j.clineuro.2004.02.013 (Pubitemid 38716160)
100. CL Hirst A Pace TP Pickersgill R Jones BN McLean, et al. 2008 Campath 1-H treatment in patients with aggressive relapsing remitting multiple sclerosis J Neurol 255 231 238 18283404 1:CAS:528:DC%2BD1cXosFGnt78%3D 10.1007/s00415-008- 0696-y
101. AJ Coles DA Compston KW Selmaj SL Lake S Moran, et al. 2008 Alemtuzumab vs. interferon beta-1a in early multiple sclerosis N Engl J Med 359 1786 1801 18946064 10.1056/NEJMoa0802670
102. JL Jones JM Anderson CL Phuah EJ Fox K Selmaj, et al. 2010 Improvement in disability after alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunity Brain 133 2232 2247 20659956 10.1093/brain/awq176
103. SA Thompson JL Jones AL Cox DA Compston AJ Coles 2010 B-cell reconstitution and BAFF after alemtuzumab (Campath-1H) treatment of multiple sclerosis J Clin Immunol 30 99 105 19763798 1:CAS:528:DC%2BC3cXhvFansbY%3D 10.1007/s10875-009-9327-3
104. MR Clatworthy EF Wallin DR Jayne 2008 Anti-glomerular basement membrane disease after alemtuzumab N Engl J Med 359 768 769 18703487 1:CAS:528: DC%2BD1cXhtVSht73P 10.1056/NEJMc0800484
105. AA Pace JP Zajicek 2009 Melanoma following treatment with alemtuzumab for multiple sclerosis Eur J Neurol 16 e70 e71 19222552 1:STN:280: DC%2BD1M3mtVKhsQ%3D%3D 10.1111/j.1468-1331.2009.02552.x
106. E Waubant 2008 Spotlight on anti-CD20 Int MS J 15 19 25 18713565 1:STN:280:DC%2BD1crjsFSqsQ%3D%3D
107. ME Reff K Carner KS Chambers PC Chinn JE Leonard, et al. 1994 Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20 Blood 83 435 445 7506951 1:CAS:528:DyaK2cXhtVCnu70%3D (Pubitemid 24030569)
108. SL Hauser E Waubant DL Arnold T Vollmer J Antel, et al. 2008 B-cell depletion with rituximab in relapsing-remitting multiple sclerosis N Engl J Med 358 676 688 18272891 1:CAS:528:DC%2BD1cXhvVehtb0%3D 10.1056/NEJMoa0706383 (Pubitemid 351240747)
109. A Bar-Or PA Calabresi D Arnold C Markowitz S Shafer, et al. 2008 Rituximab in relapsing-remitting multiple sclerosis: a 72-week, open-label, phase I trial Ann Neurol 63 395 400 18383069 1:CAS:528:DC%2BD1cXlt1Cktb4%3D 10.1002/ana.21363 (Pubitemid 351499869)
110. L Piccio RT Naismith K Trinkaus RS Klein BJ Parks, et al. 2010 Changes in B- and T-lymphocyte and chemokine levels with rituximab treatment in multiple sclerosis Arch Neurol 67 707 714 20558389 10.1001/archneurol.2010.99
111. K Hawker P O'Connor MS Freedman PA Calabresi J Antel, et al. 2009 Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial Ann Neurol 66 460 471 19847908 1:CAS:528:DC%2BD1MXhsVehtr3N 10.1002/ana.21867
112. KR Carson AM Evens EA Richey TM Habermann D Focosi, et al. 2009 Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project Blood 113 4834 4840 19264918 1:CAS:528: DC%2BD1MXmslalsbw%3D 10.1182/blood-2008-10-186999
113. MC Genovese JL Kaine MB Lowenstein J Del Giudice A Baldassare, et al. 2008 Ocrelizumab, a humanized anti-CD20 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a phase I/II randomized, blinded, placebo-controlled, dose-ranging study Arthritis Rheum 58 2652 2661 18759293 10.1002/art.23732
114. Kappos L, Calabresi P, O'Connor P, Bar-Or A, Li D, Barkhof F, Yin M, Glanzman R, Tinbergen J, Hauser S (2010) Efficacy and safety of ocrelizumab in patients with relapsing-remitting multiple sclerosis: results of a phase II randomised placebo-controlled multicentre trial. Multiple Sclerosis, Abstract at ECTRIMS 2010 (Data on file)
115. Soelberg Sorensen P, Drulovic J, Havrdova E, Lisby S, Graff O, Shackelford S (2010) Magnetic resonance imaging (MRI) efficacy of ofatumumab in relapsing-remitting multiple sclerosis (RRMS-24-week results of a phase II study. Multiple sclerosis, Abstract at ECTRIMS 2010 (Data on file)
116. A Alonso MA Hernan 2008 Temporal trends in the incidence of multiple sclerosis: a systematic review Neurology 71 129 135 18606967 10.1212/01.wnl.0000316802.35974.34