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CNS Drugs
Published in: CNS Drugs 8/2002

01-08-2002 | Review Article

Comparative Assessment of Immunomodulating Therapies for Relapsing-Remitting Multiple Sclerosis

Authors: Dr Omar Khan, Rana Zabad, Christina Caon, Marina Zvartau-Hind, Alexandros Tselis, Robert Lisak

Published in: CNS Drugs | Issue 8/2002

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Abstract

The past decade has seen unprecedented advances in the development of disease-modifying therapies for relapsing-remitting multiple sclerosis (RRMS), a disease that has a worldwide prevalence of two million patients. Four agents with the ability to modulate the immune system are now being widely used for RRMS. Of these, three are forms of interferon (IFN)-β [IFNβ-1b and two preparations of IFNβ-1a (Avonex®1 and Rebif®)], and one is a polypeptide of four amino acids (glatiramer acetate) with a unique mechanism of action. The administration regimens for the IFNβ-1 a products differ, with Avonex® being given as 30μg intramuscularly once a week and Rebif® being given as 22 or 44μg subcutaneously three times a week.
It appears safe to predict that both forms of IFNβ and glatiramer acetate will remain standard treatments for MS for years to come. However, with four therapeutic options available for RRMS, selecting a single therapy is often difficult and necessitates comparisons of the agents, which can be contentious. All four agents have shown superiority over placebo in pivotal phase III trials. Three recent prospective comparative studies have indicated that IFNβ-1b, Rebif® and glatiramer acetate may be more optimal choices than Avonex® for patients with RRMS.
In a pharmaceutical environment with an estimated worldwide market of $US2.5 billion annually for RRMS, comparative studies are understandably provocative, but at the same time provide meaningful information to clinicians and patients.
Literature
1.
Kurtzke JF. MS epidemiology world wide: one view of current status. Acta Neurol Scand 1995; 161: 23–33CrossRef
2.
Inman R. Disability indices, the economic costs of illness, and social insurance: the case of multiple sclerosis. Acta Neurol Scand 1984; 70: 46–55CrossRef
3.
Dhib-Jalbut S, McFarlin DE. Immunology of multiple sclerosis. Ann Allergy 1990; 64: 433–44PubMed
4.
Hafler DA, Weiner HL. T cells in multiple sclerosis and inflammatory central nervous system diseases. Immunol Rev 1987; 100: 308–32CrossRef
5.
McFarland HF, Dhib-Jalbut S. Multiple sclerosis: possible immunological mechanisms. Clin Immunol Immunopathol 1989; 50: S96–S105PubMedCrossRef
6.
Olsson T. Immunology of multiple sclerosis. Curr Opin Neurol Neurosurg 1992; 5: 195–202PubMed
7.
Martin R, McFarland HF, McFarlin DE. Immunological aspects of demyelinating diseases. Annu Rev Immunol 1992; 10: 153–87PubMedCrossRef
8.
Soldan SS, Jacobson S. Role of viruses in etiology and pathogenesis of multiple sclerosis. Adv Virus Res 2001; 56: 513–51
9.
Soldan SS, Betti R, Salem N, et al. Association of human herpes virus 6 (HHV-6) with multiple sclerosis: increased IgM response to HHV-6 early antigen and detection of serum HHV-6 DNA. Nat Med 1997; 3: 1394–7PubMedCrossRef
10.
Karpas A, Kampf U, Siden A, et al. Lack of evidence for involvement of known human retroviruses in multiple sclerosis. Nature 1986; 322: 177–8PubMedCrossRef
11.
Prineas JW, Raine CS. Electron microscopy and immunoperoxidase studies of early multiple sclerosis. Neurology 1976; 26: 29–32PubMedCrossRef
12.
Prineas JW. The neuropathology of multiple sclerosis. In: Koetsier JC, editor. Handbook of clinical neurology. Amsterdam: Elsevier Science Publishers, 1985; 47: 213–57
13.
Trapp BD, Peterson J, Ransohoff RM, et al. Axonal transection in the lesions of multiple sclerosis. N Engl J Med 1998; 338: 278–85PubMedCrossRef
14.
Bitsch A, Schuchardt J, Bunkowski S, et al. Axonal injury in multiple sclerosis. Correlation with demyelination and inflammation. Brain 2000; 123: 1174–83PubMedCrossRef
15.
Lucchinetti C, Bruck W, Parisi J, et al. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 2000 Jun; 47: 707–17PubMedCrossRef
16.
Weinshenker BG, Bass B, Rice GPA, et al. The natural history of multiple sclerosis: a geographically based study. I: clinical course and disability. Brain 1989; 112: 133–46PubMedCrossRef
17.
National Multiple Sclerosis Society (NMSS) compendium: early treatment. Part I: consensus statement NMSS: disease management consensus statement. New York: National Multiple Sclerosis Society, 1998 Sep 23
18.
Jacobs LD, Beck RW, Simon JH, et al. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. N Engl J Med 2000; 343: 898–904PubMedCrossRef
19.
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: 1576–82PubMedCrossRef
20.
Johnson KP, Brooks BR, Ford CC, et al. Sustained clinical benefits of glatiramer acetate in relapsing multiple sclerosis patients observed for 6 years. Mult Scler 2000; 6: 255–66PubMed
21.
The PRISMS Study Group and the University of British Columbia MS/MRI Analysis Group. PRISMS-4: long-term effect of interferon beta-1a in relapsing MS. Neurology 2001; 56: 1628–36CrossRef
22.
Isaacs A, Lindenmann J. Virus interference. I: the interferon. Proc R Soc Lond B Biol Sci 1957; 147: 258–67PubMedCrossRef
23.
Jacobs LD, O’Mailey J, Freeman A, et al. Intrathecal interferon reduces exacerbations of multiple sclerosis. Science 1981; 214: 1026–8PubMedCrossRef
24.
Jacobs LD, Salazar AM, Herndon R, et al. Intrathecally administered natural human fibroblast interferon reduces exacerbations of multiple sclerosis: results of a double-blinded study. Arch Neurol 1987; 44: 589–95PubMedCrossRef
25.
Panitch HS, Hirsch RL, Schindler J, et al. Treatment of multiple sclerosis with gamma interferon: exacerbations associated with activation of the immune system. Neurology 1987; 37: 1097–102PubMedCrossRef
26.
Durelli L, Bongioanni MR, Cavallo R, et al. Chronic systems high-dose recombinant alfa-2a reduces exacerbation rate, MRI signs of disease activity, and lymphocyte interferon gamma production in relapsing-remitting multiple sclerosis. Neurology 1994; 44: 406–13PubMedCrossRef
27.
Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33: 1444–52PubMedCrossRef
28.
Liu Z, Pelfrey CM, Cotleur A, et al. Immunomodulatory effects of interferon beta-1a in multiple sclerosis. J Neuroimmunol 2001; 112: 153–62PubMedCrossRef
29.
Kozovska ME, Hong J, Zang YC, et al. Interferon beta induces T-helper 2 immune deviation in MS. Neurology 1999; 53: 1692–7PubMedCrossRef
30.
Yong VW, Chabot S, Stuve O, et al. Interferon beta in the treatment of multiple sclerosis: mechanisms of action. Neurology 1998; 51: 682–9PubMedCrossRef
31.
Weinstock-Guttman B, Ransohoff RM, Kinkel RP, et al. The interferons: biological effects, mechanisms of action, and use in multiple sclerosis. Ann Neurol 1996; 37: 7–15CrossRef
32.
Leppert D, Waubant E, Burk MR, et al. Interferon beta-1b inhibits gelatinase secretion and in vivo migration of human T cells: a possible mechanism for treatment efficacy in multiple sclerosis. Ann Neurol 1996; 40: 846–52PubMedCrossRef
33.
Stuve 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: 853–63PubMedCrossRef
34.
Stone LA, Frank JA, Albert PS, et al. The effect of interferon beta on blood brain barrier disruptions demonstrated by contrast enhanced MRI in relapsing-remitting multiple sclerosis. Ann Neurol 1995; 37: 611–9PubMedCrossRef
35.
The IFNB 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 1993; 43: 655–61CrossRef
36.
The IFNB Study Group. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. II: MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 1993; 43: 662–7CrossRef
37.
The IFNB Study Group. Interferon beta-1b in the treatment of MS: final outcome of the randomized controlled trial. Neurology 1995; 37: 611–9
38.
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; 13: 333–40PubMedCrossRef
39.
The IFNB Study Group. Neutralizing antibodies during treatment of multiple sclerosis with interferon beta-1b: experience during the first three years. Neurology 1996; 47: 889–94CrossRef
40.
Jacobs LD, Cookfair DL, Rudick RA, et al. Intramuscular interferon beta-1 a for disease progression in relapsing multiple sclerosis. Ann Neurol 1996; 39: 285–94PubMedCrossRef
41.
Rice GPA, Ebers GC. Interferons in the treatment of multiple sclerosis. Do they prevent the progression of the disease? Arch Neurol 1998; 55: 1578–80PubMedCrossRef
42.
Rudick RA, Simonian NA, Alam JA, et al. Incidence and significance of neutralizing antibodies to interferon beta-1a in multiple sclerosis. Neurology 1998; 50: 1206–72CrossRef
43.
The PRISMS Study Group. Randomised, double-blind, placebo-controlled study of interferon beta-1a in relapsing-remitting multiple sclerosis. Lancet 1998; 352: 1498–504CrossRef
44.
Lui C, Li WPA, Blumhardt LD. Summary measure statistic for assessing outcome of treatment trials in relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 1998; 64: 726–9CrossRef
45.
Brod SA, Lindsey JW, Vriesendorp FS, et al. Ingested interferon alpha-2a: results of a pilot study in relapsing-remitting multiple sclerosis (RRMS) [abstract]. Mult Scler 2001; 7Suppl. 1: S95
46.
Noseworthy JH, Wolinsky JS, Lublin FD, et al. Linomide in relapsing and secondary progressive MS. Part I: trial design and clinical results: North American Linomide Investigators. Neurology 2000; 54: 1726–33PubMedCrossRef
47.
Noseworthy JH, O’Brien P, Erickson BJ, et al. The Mayo Clinic-Canadian Cooperative trial of sulfasalazine in active multiple sclerosis. Neurology 1998; 51: 1342–52PubMedCrossRef
48.
The Lenercept Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group. TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study. Neurology 1999; 53: 457–65CrossRef
49.
Panitch HS, Francis G and the Oral Myelin Study Group. Clinical results of a phase III trial of oral myelin in relapsing-remitting multiple sclerosis [abstract]. Ann Neurol 1997; 42: A459
50.
Kappos L, Comi G, Panitch HS, et al. Induction of a non-encephalitogenic type 2 T-helper cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo controlled, randomized phase II trial. Nat Med 2000;6: 1167–75CrossRef
51.
Medaer R, Stinissen P, Truyen L, et al. Depletion of auto-reactive myelin basic protein autoreactive T cells by T-cell vaccination: pilot trial in multiple sclerosis. Lancet 1995; 346: 807–8PubMedCrossRef
52.
Teitelbaum D, Meshorer A, Hirshfeld T, et al. Suppression of experimental allergic encephalomyelitis by a synthetic poly-peptide. Eur J Immunol 1971; 1: 242–8PubMedCrossRef
53.
Arnon R, Teitelbaum D, Sela M. Suppression of experimental allergic encephalomyelitis by Cop-1relevance to multiple sclerosis. Isr J Med Sci 1989; 25: 686–9PubMed
54.
Neuhaus O, Farina C, Wekerle H, et al. Mechanisms of action of glatiramer acetate in multiple sclerosis. Neurology 2001; 56: 702–8PubMedCrossRef
55.
Chen M, Gran B, Costello K, et al. Glatiramer acetate induces a Th2-biased response and crossreactivity with myelin basic protein in patients with MS. Mult Scler 2001; 7: 209–19PubMed
56.
Gran B, Tranquill LR, Chen M, et al. Mechanisms of immuno-modulation by glatiramer acetate. Neurology 2000; 55: 1704–14PubMedCrossRef
57.
Duda PW, Krieger JI, Schmied MC, et al. Human and murine CD4 T cell reactivity to a complex antigen: recognition of the synthetic random polypeptide glatiramer acetate. J Immunol 2000; 165: 7300–7PubMed
58.
Aharoni R, Teitelbaum D, Leitner O, et al. Specific Th2 cells accumulate in the central nervous system of mice protected against experimental autoimmune encephalomyelitis by copolymer 1. Proc Natl Acad Sci U S A 2000; 97(21): 11472–7PubMedCrossRef
59.
Kipnis J, Yoles E, Porat Z, et al. T cell immunity to copolymer 1 confers neuroprotection on the damaged optic nerve: possible therapy for optic neuropathies. Proc Natl Acad Sci U S A 2000; 97: 7446–51PubMedCrossRef
60.
Bornstein MB, Miller AI, Teitelbaum D, et al. Multiple sclerosis: a trial of synthetic polypeptide. Ann Neurol 1982; 11:317–9PubMedCrossRef
61.
Bornstein MB, Miller AI, Slagle S, et al. A pilot trial of Cop 1 in exacerbating-remitting multiple sclerosis. N Engl J Med 1987; 317: 408–14PubMedCrossRef
62.
Johnson KP, Brooks BR, Cohen JA, et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind, placebo-controlled trial. Neurology 1995; 45: 1268–76PubMedCrossRef
63.
Cohen JA, Grossman R, Udupa J, et al. Assessment of the efficacy of copolymer-1 in the treatment of relapsing-remitting multiple sclerosis by quantitative MRI [abstract]. Neurology 1995; 45Suppl. 4: A418
64.
Johnson KP, Brooks BR, Cohen JA, 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 1998; 50: 710–08
65.
Comi G, Filippi M, Wolinsky JS, et al. 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. Ann Neurol 2001; 49: 290–7PubMedCrossRef
66.
Filippi M, Rovaris M, Rocca M, et al. Glatiramer acetate reduces the proportion of new MS lesions evolving into “black holes”. Neurology 2001; 57: 731–3PubMedCrossRef
67.
Van Waesberghe JH, Kamphorst W, De Groot CJ, et al. Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability. Ann Neurol 1999; 46: 747–54PubMedCrossRef
68.
Bitsch A, Kuhlman T, Stadelman C, et al. A longitudinally MRI study of histopathologically defined hypointense multiple sclerosis lesions. Ann Neurol 2001; 49: 793–6PubMedCrossRef
69.
Chan KB, Man-Son-Hing M, Molnar FJ, et al. How well is the clinical importance of study results reported? An assessment of randomized controlled trials. CMAJ 2001; 165: 1197–202PubMed
70.
Concato J, Shah N, HorwitzR I. Randomized, controlled trials, observational studies, and the hierarchy of research designs. N Engl J Med 2000; 342: 1887–92PubMedCrossRef
71.
Benson K, Hartz AJ. A comparison of observational studies and randomized, controlled trials. N Engl J Med 2000; 342: 1878–86PubMedCrossRef
72.
Black N. Why do we need observational studies to evaluate the effectiveness of health care? BMJ 1996; 312: 215–8CrossRef
73.
Khan OA, Tselis AC, Kamholz J, et al. A prospective open-label treatment trial to compare the effect of IFNbeta-1a (Avonex), IFNbeta-1b (Betaseron), and glatiramer acetate (Copaxone) on the relapse rate in relapsing-remitting multiple sclerosis. Eur J Neurol 2001; 8: 141–8PubMedCrossRef
74.
Khan OA, Tselis AC, Kamholz JA, et al. A prospective, open-label treatment trial to compare the effect of IFN beta-1a (Avonex), IFN beta-1b (Betaseron), and glatiramer acetate (Copaxone) on the relapse rate in relapsing-remitting multiple sclerosis: results after 18 months of therapy. Mult Scler 2001 Dec; 7: 349–53PubMed
75.
Durelli L, Ferrero B, Ghezi A, et al. The Independent Comparison of Interferon (INCOMIN) Trial: a multicenter randomized trial comparing clinical and MRI efficacy of IFN beta-1a and IFN beta-1b in multiple sclerosis [abstract]. Neurology 2001;56Suppl. 3: A148
76.
Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983; 13: 227–31PubMedCrossRef
77.
Durelli L, Verdun E, Barbero P, et al. The independent comparison of interferon (INCOMIN) trial: final long-term results [abstract]. Neurology 2002; 58Suppl. 3: A86
78.
Witt PL, Storer BE, Bryan GT, et al. Pharmacodynamics of biological response in vivo after single and multiple doses of interferon beta. J Immunother 1993; 13: 191–200CrossRef
79.
OWIMS STUDY Group. Evidence of interferon beta-1a dose response in relapsing-remitting MS: the OWIMS study. Neurology 1999; 53: 679–86CrossRef
80.
Williams GJ, Witt PL. Comparative effects of Betaseron and Avonex. J Interferon Res 1998; 18: 967–75
81.
Coyle P. Results of comparative efficacy trials using two formulations of interferon beta-1a in RRMS. J Neurol Sci 2001; 187Suppl. 1: S436
82.
Panitch H, Coyle P, Francis G, et al. The evidence of interferon dose response: European-North American comparative efficacy (EVIDENCE) study: 48 week data [abstract]. Neurology 2002; 58Suppl. 3: A86–7
Metadata
Title
Comparative Assessment of Immunomodulating Therapies for Relapsing-Remitting Multiple Sclerosis
Authors
Dr Omar Khan
Rana Zabad
Christina Caon
Marina Zvartau-Hind
Alexandros Tselis
Robert Lisak
Publication date
01-08-2002
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 8/2002
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.2165/00023210-200216080-00005

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