Skip to main content
Log in

Interferons in Relapsing-Remitting Multiple Sclerosis

Are There Benefits from Long-Term Use?

  • Current Opinion
  • Published:
CNS Drugs Aims and scope Submit manuscript

Abstract

Multiple sclerosis (MS) is one of the most common chronic neurological diseases in young adults in western countries. An important aspect of treatment of this disease is the use of interferons (IFNs). These are molecules with antiviral, immunomodulatory, antiproliferative and hormonal activities. IFNβ, a class I IFN, has been used extensively in the therapy of MS, particularly in its relapsing-remitting (RRMS) phase, the most frequent clinical form of the disease.

Although the available evidence from published clinical trials is difficult to evaluate because of methodological differences, an unbiased review of the data reveals sufficient evidence to conclude that treatment with IFNβ in RRMS is both efficacious and safe, at least over the periods so far investigated (up to 4–6 years). While there is no reason to suspect that IFNβ should not continue to be efficacious and safe over the longer term, studies investigating these questions over longer periods and including greater numbers of patients are needed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Table I
Table II
Table III
Table IV
Fig. 1

Similar content being viewed by others

References

  1. Noseworthy JH, Lucchinetti C, Rodriguez M, et al. Multiple sclerosis. New Engl J Med 2000; 343: 938–52

    Article  PubMed  CAS  Google Scholar 

  2. Trapp BD, Peterson J, Ransohoff RM, et al. Axonal transection in lesions of multiple sclerosis. New Engl J Med 1998; 338: 278–85

    Article  PubMed  CAS  Google Scholar 

  3. Lucchinetti C, Brück W, Parisi J, et al. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 2000; 47: 707–17

    Article  PubMed  CAS  Google Scholar 

  4. Bitsch A, Bruck W. Differentiation of multiple sclerosis subtypes: implications for treatment. CNS Drugs 2002; 16(6): 405–18

    Article  PubMed  CAS  Google Scholar 

  5. Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. Neurology 1996; 46: 906–11

    Google Scholar 

  6. Johnson HM, Bazer FW, Szente BE, et al. How interferons fight disease. Sci Am 1994; 270: 40–7

    Article  Google Scholar 

  7. Isaacs A, Lindenmann J. Virus interference:1. The interferon. Proc R Soc Lond B Biol Sci 1957; 147: 258–67

    Article  CAS  Google Scholar 

  8. Pestka S, Langer JA, Zoon KC, et al. Interferons and their actions. Annu Rev Biochem 1987; 56: 727–77

    Article  PubMed  CAS  Google Scholar 

  9. Fleischmann WR, Ramamurthy V, Stanton JG, et al. Interferon: mode of action and clinical applications. In: Smith RA, editor. Interferon treatment of neurologic disorders. New York: Marcel Dekker, 1988: 1–42

    Google Scholar 

  10. De Mayer E, De Mayer-Guignard J, editors. The interferon gene family. In: Interferons and other regulatory cytokines. New York: John Wiley & Sons, 1988: 5–38

  11. Ealick SE, Coock WJ, Vijay-Kumar S, et al. Three-dimensional structure of recombinant interferon-gamma. Science 1991; 252: 698–702

    Article  PubMed  CAS  Google Scholar 

  12. Farrar MA, Schreiber RD. The molecular cell biology of interferon-gamma and its receptor. Annu Rev Immunol 1993; 11: 571–611

    Article  PubMed  CAS  Google Scholar 

  13. Weinstock-Guttman B, Ransohoff RM, Kinkel RP, et al. The interferons: biological effects, mechanisms of action, and use in multiple sclerosis. Ann Neurol 1995; 37: 7–15

    Article  PubMed  CAS  Google Scholar 

  14. Pestka S. The purification and manufacture of human interferons. Sci Am 1983; 249: 36–43

    Article  CAS  Google Scholar 

  15. Neighbour PA, Miller AE, Bloom BR. Interferon responses of leukocytes in multiple sclerosis. Neurology 1981; 31: 561–6

    Article  PubMed  CAS  Google Scholar 

  16. Neighbour PA. Studies of interferon production and natural killing by lymphocytes from multiple sclerosis patients. Ann N Y Acad Sci 1984; 436: 181–91

    Article  PubMed  CAS  Google Scholar 

  17. Barna BP, Chou SM, Jacobs B, et al. Interferon-B impairs induction of HLA-DR antigen expression in cultured human astrocytes. J Neuroimmunol 1989; 23: 45–53

    Article  PubMed  CAS  Google Scholar 

  18. Abreu SL. Suppression of experimental allergic encephalomyelitis by interferon. Immunol Invest 1982; 11: 1–7

    Article  CAS  Google Scholar 

  19. Hertz F, Deghenghi R. Effect of rat and beta human interferon on hyperacute experimental allergic encephalomyelitis in rats. Agents Actions 1985; 16: 397–403

    Article  PubMed  CAS  Google Scholar 

  20. Noronha A, Toscas A, Jensen MA. Interferon beta augments suppressor cell function in multiple sclerosis. Ann Neurol 1990; 27: 207–10

    Article  PubMed  CAS  Google Scholar 

  21. Leppert D, Waubant E, Biirk MR, et al. Interferon beta-1b inhibits gelatinase secretion and in vitro migration of human T cells: a possible mechanism for treatment efficacy in multiple sclerosis. Ann Neurol 1996; 40: 846–52

    Article  PubMed  CAS  Google Scholar 

  22. Stüve O, Dooley NP, Uhm JH, et al. Interferon beta-lb decreases the migration of T lymphocytes in vitro: effects on matrix metalloproteinase-9. Ann Neurol 1996; 40: 853–63

    Article  PubMed  Google Scholar 

  23. Porrini AM, Gambi D, Reder AT. Interferon effects on interleukin-10 secretion: mononuclear cell response to interleukin-10 is normal in multiple sclerosis patients. J Neuroimmunol 1995; 61: 27–34

    Article  PubMed  CAS  Google Scholar 

  24. Zang YC, Yang D, Hong J, et al. Immunoregulation and blocking antibodies induced by interferon beta treatment in MS. Neurology 2000; 55: 397–404

    Article  PubMed  CAS  Google Scholar 

  25. Stewart VC, Land JM, Clark JB, et al. Pretreatment of astrocytes with interferon alfa/beta prevents neuronal mitochondrial respiratory chain damage. J Neurochem 1998; 70: 432–4

    Article  PubMed  CAS  Google Scholar 

  26. Merrill JE, Targan SR. The immunological basis for the use of interferons. In: Smith RA, editor. Interferon treatment of neurological disorders. New York: Marcel Dekker, 1988, 101

    Google Scholar 

  27. Yong VW. Differential mechanisms of action of interferon-beta and glatiramer acetate in MS. Neurology 2002; 59: 802–8

    Article  PubMed  CAS  Google Scholar 

  28. Dhib-Jalbut S. Mechanisms of action of interferons and glatiramer acetate in multiple sclerosis. Neurology 2002; 58: S3–9

    Article  PubMed  CAS  Google Scholar 

  29. Liu Z, Pelfrey CM, Cotleur A, et al. Immunomodulatory effects of interferon beta-la in multiple sclerosis. J Neuroimmunol 2001; 112: 153–62

    Article  PubMed  CAS  Google Scholar 

  30. Gelati M, Corsini E, Dufour A, et al. Immunological effects of in vivo interferon-betalb treatment in ten patients with multiple sclerosis: a 1-year follow-up. J Neurol 1999; 246: 569–73

    Article  PubMed  CAS  Google Scholar 

  31. Calabresi PA, Pelfrey CM, Tranquill LR, et al. VLA-4 expression on peripheral blood lymphocytes is downregulated after treatment of multiple sclerosis with interferon beta. Neurology 1997; 49: 1111–6

    Article  PubMed  CAS  Google Scholar 

  32. Lou J, Gasche Y, Zheng L, et al. Interferon-beta inhibits activated leukocyte migration through human brain microvascular endothelial cell monolayer. Lab Invest 1999; 79:1015–25

    PubMed  CAS  Google Scholar 

  33. Rudick RA, Ransohoff RM, Peppier R, et al. Interferon beta induces interleukin-10 expression: relevance to multiple sclerosis. Ann Neurol 1996; 40: 618–27

    Article  PubMed  CAS  Google Scholar 

  34. Wang X, Chen M, Wandinger KP, et al. IFNbeta-1b inhibits IL-12 production in peripheral blood mononuclear cells in an IL-10-dependent mechanism: relevance to IFNbeta-lb therapeutic effects in multiple sclerosis. J Immunol 2000; 165: 548–57

    PubMed  CAS  Google Scholar 

  35. Miller A, Lanir N, Shapiro S, et al. Immunoregulatory effects of interferon-beta and interacting cytokines on human vascular endothelial cells: implications for multiple sclerosis autoimmune diseases. J Neuroimmunol 1996; 64: 151–61

    Article  PubMed  CAS  Google Scholar 

  36. Noronha A, Toscas A, Jensen MA. Interferon beta decreases T cell activation and interferon gamma production in multiple sclerosis. J Neuroimmunol 1993; 46: 145–53

    Article  PubMed  CAS  Google Scholar 

  37. Gene K, Dona DL, Reder AT. Increased CD80(+) B cells in active multiple sclerosis and reversal by interferon beta-1b therapy. J Clin Invest 1997; 99: 2664–71

    Article  Google Scholar 

  38. Hall GL, Compston A, Scolding NJ. Beta-interferon and multiple sclerosis. Trends Neurosci 1997; 20: 63–7

    Article  PubMed  CAS  Google Scholar 

  39. Narayanan S, De Stefano N, Francis GS, et al. Axonal metabolic recovery in multiple sclerosis patients treated with interferon beta-1b. J Neurol 2001; 248: 979–86

    Article  PubMed  CAS  Google Scholar 

  40. Jacobs LD, Beck RW, Simon JH, et al. and the CHAMPS Study Group. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. N Engl J Med 2000; 343: 898–904

    CAS  Google Scholar 

  41. Beck RW, Chandler DL, Cole SR, et al. Interferon beta-1a for early multiple sclerosis: CHAMPS trial subgroup analysis. Ann Neurol 2002; 51: 481–90

    Article  PubMed  CAS  Google Scholar 

  42. Comi G, Filippi M, Barkhof F, et al. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 2001; 357: 1576–82

    Article  PubMed  CAS  Google Scholar 

  43. Fernandez O, Antiguedad A, Arbizu T, et al. Treatment of relapsing-remitting multiple sclerosis with natural interferon beta: a multicenter, randomized clinical trial. Mult Scler 1995; 1Suppl. 1: S67–9

    PubMed  CAS  Google Scholar 

  44. Fernandez O, Antiguedad A, Arbizu T, et al. Natural interferon-beta in the treatment of relapsing-remitting multiple sclerosis: a multicenter, randomized, MRI-based, phase II clinical trial. Rev Neurol 1999 Dec 16–31; 29(12): 1093–9

    PubMed  CAS  Google Scholar 

  45. Patti F, L’Episcopo MR, Cataldi ML, et al. Natural interferon-beta treatment of relapsing-remitting and secondary-progressive multiple sclerosis patients: a two-year study. Acta Neurol Scand 1999 Nov; 100(5): 283–9

    Article  PubMed  CAS  Google Scholar 

  46. Knobler RL, Greenstein JI, Johnson KP, et al. Systemic recombinant human interferon-beta treatment of relapsing-remitting multiple sclerosis: pilot study analysis and six-year follow-up. J Interferon Res 1993 Oct; 13(5): 333–40

    Article  PubMed  CAS  Google Scholar 

  47. Pozzilli C, Bastianello S, Koudriavtseva T, et al. Magnetic resonance imaging changes with recombinant human interferon-β-la: a short term study in relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 1996; 61(3): 251–8

    Article  PubMed  CAS  Google Scholar 

  48. Paolillo A, Pozzilli C, Giugni E, et al. A 6-year clinical and MRI follow-up study of patients with relapsing-remitting multiple sclerosis treated with interferon-beta. Eur J Neurol 2002 Nov; 9(6): 645–55

    Article  PubMed  CAS  Google Scholar 

  49. The IFNB Multiple Sclerosis Study Group. Interferon beta-lb is effective in relapsing-remitting multiple sclerosis: I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 1993; 43: 655–61

    Google Scholar 

  50. Paty DW, Li DKB, the UBC MS/MRI Study Group, the Multiple Sclerosis Study Group. Interferon beta-lb is effective in relapsing-remitting multiple sclerosis: II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 1993; 43: 662–7

    Article  PubMed  CAS  Google Scholar 

  51. The IFNB Multiple Sclerosis Study Group, the University of British Columbia MS/MRI Analysis Group. Interferon beta-lb in the treatment of multiple sclerosis: final outcome of the randomised controlled trial. Neurology 1995; 45: 1277–85

    Article  Google Scholar 

  52. Jacobs LD, Cookfair DL, Rudick RA, et al. Intramuscular interferon beta-la for disease progression in relapsing multiple sclerosis. Ann Neurol 1996; 39: 285–94

    Article  PubMed  CAS  Google Scholar 

  53. Simon JH, Lawrence L, Campion M, et al. Magnetic resonance studies of intramuscular interferon beta-la for relapsing multiple sclerosis. Ann Neurol 1998; 43: 79–87

    Article  PubMed  CAS  Google Scholar 

  54. Rudick RA, Fisher E, Lee JC, et al. and the Multiple Sclerosis Collaborative Research Group. Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Neurology 1999; 53: 1698–704

    CAS  Google Scholar 

  55. PRISMS (Prevention of Relapses and Disability by Interferon β-1a Subcutaneously in Multiple Sclerosis) Study Group. Randomised double-blind placebo-controlled study of interferon-β-1a in relapsing-remitting multiple sclerosis. Lancet 1998; 352: 1498–504

    Article  Google Scholar 

  56. The PRISMS Study Group, the University of British Columbia MS/MRI Analysis Group. PRISMS-4: long-term efficacy of interferon-beta-1a in relapsing MS. Neurology 2001; 56:1628–36

    Article  Google Scholar 

  57. The Once Weekly Interferon for MS study group (OWIMS). Evidence of interferon β-1a dose response in relapsing-remitting MS. Neurology 1999; 53: 679–86

    Article  Google Scholar 

  58. Comi G, Inglese M, De Stefano N, et al. Brain volume changes in patients at presentation with suspected multiple sclerosis: results from the ETOMS study. J Neurol 2002; 249Suppl. 1:I/21

    Google Scholar 

  59. Gasperini C, Paolillo A, Giugni E, et al. MRI brain volume changes in relapsing-remitting multiple sclerosis patients treated with interferon beta-1a. Mult Scler 2002; 8: 119–23

    Article  PubMed  CAS  Google Scholar 

  60. Jones CK, Riddenhough A, Li DKB, et al. MRI cerebral atrophy in relapsing-remitting MS: results from the PRISMS trial. Neurology 2001; 56Suppl. 3: A379

    Google Scholar 

  61. Clanet M, Radue EW, Kappos LL, et al. A randomised, double-blind, dose-comparison study of weekly interferon beta-1a in relapsing MS. Neurology 2002; 59: 1507–17

    Article  PubMed  CAS  Google Scholar 

  62. Panitch H, Goodin DS, Francis G, et al. Randomised, comparative study of interferon β-1a treatment regimens in MS: the EVIDENCE trial. Neurology 2002; 59: 1496–506

    Article  PubMed  CAS  Google Scholar 

  63. Durelli L, Verdun E, Barbero P, et al. Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis: results of a 2-year prospective randomised multi-centre study (INCOMIN). Lancet 2002; 359: 1453–60

    Article  PubMed  CAS  Google Scholar 

  64. European Study Group on Interferon β-1b in Secondary Progressive MS. Placebo-controlled multicentre randomised trial of inteferon β-1b in treatment of secondary progressive multiple sclerosis. Lancet 1998; 352: 1491–97

    Article  Google Scholar 

  65. Kappos L, Polman C, Pozzilli C, et al. Final analysis of the European multicenter trial on IFNbeta-1b in secondary-progressive MS. Neurology 2001; 57: 1969–75

    Article  PubMed  CAS  Google Scholar 

  66. Goodkin DE, the North American Study Group on Interferon beta-1b in Secondary Progressive MS. The North American Study of Interferon beta-1b in Secondary Progressive Multiple Sclerosis. The 52nd Annual Meeting of the American Academy of Neurology; 2000 May 1, San Diego

  67. Secondary Progressive Efficacy Clinical Trial of Recombinant Interferon-beta-1a in MS (SPECTRIMS) Study Group. Randomised controlled trial of interferon-beta-1a in secondary progressive MS: clinical results. Neurology 2001; 56: 1496–504

    Article  Google Scholar 

  68. Li DK, Zhao GJ, Paty DW. Randomised controlled trial of interferon-beta-la in secondary progressive MS: MRI results. Neurology 2001; 56: 1505–13

    Article  PubMed  CAS  Google Scholar 

  69. Cohen JA, Cutter GR, Fischer JS, et al. Benefit of interferon beta-1a on MSFC progression in secondary progressive MS. Neurology 2002; 59: 679–87

    Article  PubMed  CAS  Google Scholar 

  70. Leary SM, Miller DH, Stevenson VL, et al. Interferon beta-1a in primary progressive MS: an exploratory, randomised, controlled trial. Neurology 2003; 60: 44–51

    Article  PubMed  CAS  Google Scholar 

  71. Montalban X, Brieva L, Tintoré M, et al. Single center, DBPC, randomised trial of interferon betalb in primary progressive and transitional progressive multiple sclerosis: an exploratory phase II study [abstract no. LB5 ACTRIMS-ECTRIMS 2002]. Abstract Viewer. London: MS Journal CD-ROM

  72. Ruggieri RM, Settipani N, Viviano L, et al. Long-term interferon-beta treatment for multiple sclerosis. Neurol Sci 2003; 24: 361–4

    Article  PubMed  CAS  Google Scholar 

  73. Grigoriadis N. Interferon beta treatment in relapsing-remitting multiple sclerosis: a review. Clin Neurol Neurosurg 2002 Jul; 104(3): 251–8

    Article  PubMed  Google Scholar 

  74. Chofflon M, Ben-Amor AF. Long-term benefits of early and high doses of interferon beta-1a treatment in relapsing-remitting multiple sclerosis. Lancet 2003; 361: 542–5

    Article  Google Scholar 

  75. Calabresi PA. Considerations in the treatment of relapsing-remitting multiple sclerosis. Neurology 2002 Apr 23; 58(8 Suppl. 4): S10–22

    Article  PubMed  CAS  Google Scholar 

  76. O’Connor P, the Canadian Multiple Sclerosis Working Group. Key issues in the diagnosis of multiple sclerosis: an overview. Neurology 2002; 59Suppl. 3: S1–33

    Article  PubMed  Google Scholar 

  77. Goodin DS, Frohman EM, Garmany GP, et al. Disease modifying therapies in multiple sclerosis: subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology 2002; 58: 169–78

    Article  PubMed  CAS  Google Scholar 

  78. Rice GP, Incorvaia B, Munari L, et al. Interferon in relapsing-remitting multiple sclerosis. Cochrane Database Syst Rev 2001; (4): CD002002

  79. Filippini G, Munari L, Incorvaia B, et al. Interferons in relapsing remitting multiple sclerosis: a systematic review. Lancet 2003; 361: 545–52

    Article  PubMed  CAS  Google Scholar 

  80. Durelli L, Bongioanni MR, Cavallo R, 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 1994 Mar; 44 (3 Pt 1): 406–13

    Article  PubMed  CAS  Google Scholar 

  81. Myhr KM, Riise T, Green Lilleas FE, et al. Interferon-alpha2a reduces MRI disease activity in relapsing-remitting multiple sclerosis. Norwegian Study Group on Interferon-alpha in Multiple Sclerosis. Neurology 1999 Mar 23; 52(5): 1049–56

    Article  PubMed  CAS  Google Scholar 

  82. Kolar OJ, Bauerle JA, Lee H. Interferons in relapsing remitting multiple sclerosis [letter]. Lancet 2003 May 24; 361(9371): 1825

    Article  PubMed  Google Scholar 

  83. Rudick RA, Cookfair DL, Griffin J, et al. Interferons in relapsing remitting multiple sclerosis. Lancet 2003 May 24; 361(9371): 1824–5

    Article  PubMed  Google Scholar 

  84. Paty D, Arnason B, Li D, et al. Interferons in relapsing remitting multiple sclerosis. Lancet 2003 May 24; 361(9371): 1822; 1823-4

    Article  PubMed  Google Scholar 

  85. Freedman M, King J, Oger J, et al. for the PRISMS Study Investigators. Interferons in relapsing remitting multiple sclerosis. Lancet 2003 May 24; 361(9371): 1822–3

    Google Scholar 

  86. Kappos L, Kesselring J. Interferons in relapsing remitting multiple sclerosis. Lancet 2003 May 24; 361(9371): 1821–2

    Article  PubMed  Google Scholar 

  87. Goodin DS. Interferons in relapsing remitting multiple sclerosis [letter]. Lancet 2003 May 24; 361(9371): 1821

    Article  PubMed  Google Scholar 

  88. Filippini G, Munari L, Ebers G, et al. Interferons in relapsing remitting multiple sclerosis. Lancet 2003 May 24; 361:1823–5

    Article  Google Scholar 

  89. Rio J, Nos C, Bonaventura I. Corticosteroids, ibuprofen and acetaminophen for IFN beta-1a flu symptoms in MS: a randomized trial. Neurology 2004; 63: 525–8

    Article  PubMed  CAS  Google Scholar 

  90. Bertolotto A, Malucchi S, Sala A, et al. Differential effects of three interferon betas on neutralising antibodies in patients with multiple sclerosis: a follow up study in an independent laboratory. J Neurol Neurosurg Psychiatry 2002; 73: 148–53

    Article  PubMed  CAS  Google Scholar 

  91. Bellomi F, Scagnolari C, Tomassini V, et al. Fate of neutralizing and binding antibodies to IFN beta in MS patients treated with IFN beta for 6 years. J Neurol Sci 2003; 215: 3–8

    Article  PubMed  CAS  Google Scholar 

  92. Sorensen S, Ross C, Clemmesen KM, et al. Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis. Lancet 2003; 362: 1184–91

    Article  PubMed  CAS  Google Scholar 

  93. Perini P, Calabrese M, Biasi G, et al. The clinical impact of interferon beta antibodies in relapsing-remitting MS. J Neurol 2004; 251: 305–9

    Article  PubMed  CAS  Google Scholar 

  94. Fierlbeck G, Schreiner T. Incidence and clinical significance of therapy-induced neutralizing antibodies against interferon-B. J Interferon Res 1994; 14: 205–6

    Article  PubMed  CAS  Google Scholar 

  95. Antonelli G, Bagnato F, Pozzilli C, et al. Development of neutralizing antibodies in patients with relapsing-remitting multiple sclerosis treated with IFNB 1a. J Interferon Cytokine Res 1998; 18: 345–50

    Article  PubMed  CAS  Google Scholar 

  96. Pachner AR. Anti-IFNB antibodies in IFNB-treated MS patients. Neurology 2003; 61Suppl. 5: Sl–39

    Google Scholar 

  97. Mayorga C, Luque G, Romero F, et al. Antibodies to commercially available interferon-beta molecules in multiple sclerosis patients treated with natural interferon-beta. Int Arch Allergy Immunol 1999; 118: 368–71

    Article  PubMed  CAS  Google Scholar 

  98. Fernandez O, Mayorga C, Luque G, et al. Study of binding and neutralising antibodies to interferon-beta in two groups of relapsing-remitting multiple sclerosis patients. J Neurol 2001 May; 248(5): 383–8

    Article  PubMed  CAS  Google Scholar 

  99. Kivisakk P, Alm GV, Fredrikson S, et al. Neutralizing and binding anti-interferon-beta (IFNbeta) antibodies: a comparison between IFNbeta-1a and IFNbeta-1b treatment in multiple sclerosis. Eur J Neurol 2000; 7: 27–34

    Article  PubMed  CAS  Google Scholar 

  100. 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-1b: experience during the first three years. Neurology 1996; 47: 889–94

    Article  Google Scholar 

  101. Paty DW, Goodkin D, Thompson A, et al. Guidelines for physicians with patients on IFNβ-1b: the use of an assay for neutralizing antibodies (NAB). Neurology 1996; 47: 865–6

    Article  PubMed  CAS  Google Scholar 

  102. Mayorga C, Luque G, Bianca M, et al. Antibodies to the IFNβ commercially available molecules in multiple sclerosis patients treated with natural IFNβ [abstract]. Mult Scler 1998; 4: S379

    Google Scholar 

  103. Rice GP, Oger J, Duquette P, et al. Treatment with interferon beta-1b improves quality of life in multiple sclerosis. Can J Neurol Sci 1999; 26(4): 276–82

    PubMed  CAS  Google Scholar 

  104. Nortvedt MW, Riise T. The use of quality of life measures in multiple sclerosis research. Mult Scler 2003 Feb; 9(1): 63–72

    Article  PubMed  CAS  Google Scholar 

  105. Fernandez O, Arbizu T, Izquierdo G, et al. Clinical benefits of interferon beta-1a in relapsing-remitting MS: a phase IV study. Acta Neurol Scand 2003; 107: 7–11

    Article  PubMed  CAS  Google Scholar 

  106. Dubois BD, Keenan E, Porter BE, et al. Interferon beta in multiple sclerosis: experience in a British specialist multiple sclerosis centre. J Neurol Neurosurg Psychiatry 2003 Jul; 74(7): 946–9

    Article  PubMed  CAS  Google Scholar 

  107. Arbizu T, Alvarez-Cermeno JC, Decap G, et al. Interferon beta-1b treatment in patients with relapsing: remitting multiple sclerosis under a standardized protocol in Spain. Acta Neurol Scand 2000 Oct; 102(4): 209–17

    Article  PubMed  CAS  Google Scholar 

  108. Trojano M, Liguori M, Paolicelli D, et al. Inteferon beta in relapsing-remitting multiple sclerosis: an independent post-marketing study in southern Italy. Mult Scler 2003; 9: 451–7

    Article  PubMed  CAS  Google Scholar 

  109. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33: 1444–52

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The author did not receive any funding in preparing this manuscript. He has participated or is currently participating in clinical trials by Bayer, Biogen, Schering A. G., Serono, Teva, Wyeth and Novartis.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Oscar Fernández.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fernández, O. Interferons in Relapsing-Remitting Multiple Sclerosis. CNS Drugs 18, 1057–1070 (2004). https://doi.org/10.2165/00023210-200418150-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00023210-200418150-00002

Keywords

Navigation