Skip to main content
Neurotherapeutics logoLink to Neurotherapeutics
. 2007 Oct;4(4):633–646. doi: 10.1016/j.nurt.2007.07.001

Interferon-β treatment for multiple sclerosis

Robert A Bermel 1, Richard A Rudick 1,
PMCID: PMC7479675  PMID: 17920544

Summary

Multiple sclerosis (MS) is the leading nontraumatic cause of neurologic disability in young adults. Interferon-β, approved for use in 1993, was the first treatment to modify the course and prognosis of the disease and remains a mainstay of MS treatment. Numerous large-scale clinical trials in early, active patient populations have established the clinical efficacy of interferon-β in reducing relapses and delaying disability progression. Although its mechanism of action remains incompletely understood, a reduction in active lesions seen on magnetic resonance imaging implies primary anti-inflammatory properties, a mechanism supported by basic immunologic research. Variation in individual patient responsiveness to interferon-β may be due to disease variability or differential induction of interferon-stimulated genes. The magnitude of the therapeutic effect appears to be similar among products, but the optimal dose, route, and frequency of administration of the drug remain uncertain.

Key Words: interferon, multiple sclerosis, clinical trials

References

  • 1.Whetten-Goldstein K, Sloan FA, Goldstein LB, Kulas ED. A comprehensive assessment of the cost of multiple sclerosis in the United States. Mult Scler. 1998;4:419–425. doi: 10.1177/135245859800400504. [DOI] [PubMed] [Google Scholar]
  • 2.Charcot JM. Histologie de la sclérose en plaques. [In French] Gazette des hôpitaux, Paris. 1868;41:554–555. [Google Scholar]
  • 3.Weinstock-Guttman B, Ransohoff RM, Kinkel RP, Rudick RA. The interferons: biological effects, mechanisms of action, and use in multiple sclerosis. Ann Neurol. 1995;37:7–15. doi: 10.1002/ana.410370105. [DOI] [PubMed] [Google Scholar]
  • 4.Isaacs A, Lindenmann J. Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci. 1957;147:258–267. doi: 10.1098/rspb.1957.0048. [DOI] [PubMed] [Google Scholar]
  • 5.Tourtellotte WW, Walsh MJ, Baumhefner RW, Staugaitis SM, Shapshak P. The current status of multiple sclerosis intra-blood-brain-barrier IgG synthesis. Ann N Y Acad Sci. 1984;436:52–67. doi: 10.1111/j.1749-6632.1984.tb14775.x. [DOI] [PubMed] [Google Scholar]
  • 6.Neighbour PA, Miller AE, Bloom BR. Interferon responses of leukocytes in multiple sclerosis. Neurology. 1981;31:561–566. doi: 10.1212/wnl.31.5.561. [DOI] [PubMed] [Google Scholar]
  • 7.Panitch HS, Hirsch RL, Schindler J, Johnson KP. Treatment of multiple sclerosis with gamma interferon: exacerbations associated with activation of the immune system. Neurology. 1987;37:1097–1102. doi: 10.1212/wnl.37.7.1097. [DOI] [PubMed] [Google Scholar]
  • 8.Jacobs L, Johnson KP. A brief history of the use of interferons as treatment of multiple sclerosis. Arch Neurol. 1994;51:1245–1252. doi: 10.1001/archneur.1994.00540240089022. [DOI] [PubMed] [Google Scholar]
  • 9.Jacobs L, O’Malley J, Freeman A, Ekes R, Reese PA. Intrathecal interferon in multiple sclerosis. Arch Neurol. 1982;39:609–615. doi: 10.1001/archneur.1982.00510220007002. [DOI] [PubMed] [Google Scholar]
  • 10.Trapp BD, Ransohoff RM, Fisher E, Rudick RA. Neurodegeneration in multiple sclerosis: relationship to neurological disability. Neuroscientist. 1999;5:48–57. doi: 10.1177/107385849900500107. [DOI] [Google Scholar]
  • 11.Yong VW, Chabot S, Stuve O, Williams G. Interferon beta in the treatment of multiple sclerosis: mechanisms of action. Neurology. 1998;51:682–689. doi: 10.1212/wnl.51.3.682. [DOI] [PubMed] [Google Scholar]
  • 12.Noronha A, Toscas A, Jensen MA. Interferon beta decreases T cell activation and interferon gamma production in multiple sclerosis. J Neuroimmunol. 1993;46:145–153. doi: 10.1016/0165-5728(93)90244-S. [DOI] [PubMed] [Google Scholar]
  • 13.Karp CL, van Boxel-Dezaire AH, Byrnes AA, Nagelkerken L. Interferon-beta in multiple sclerosis: altering the balance of interleukin-12 and interleukin-10? Curr Opin Neurol. 2001;14:361–368. doi: 10.1097/00019052-200106000-00016. [DOI] [PubMed] [Google Scholar]
  • 14.Ransohoff RM. Biological responses to type I interferons: relationship to therapeutic effects in multiple sclerosis. London: Martin Dunitz; 2003. [Google Scholar]
  • 15.Stone LA, Frank JA, Albert PS, et al. The effect of interferon-beta on blood-brain barrier disruptions demonstrated by contrast-enhanced magnetic resonance imaging in relapsing-remitting multiple sclerosis. Ann Neurol. 1995;37:611–619. doi: 10.1002/ana.410370511. [DOI] [PubMed] [Google Scholar]
  • 16.Calabresi PA, Tranquill LR, Dambrosia JM, et al. Increases in soluble VCAM-1 correlate with a decrease in MRI lesions in multiple sclerosis treated with interferon beta-1b. Ann Neurol. 1997;41:669–674. doi: 10.1002/ana.410410517. [DOI] [PubMed] [Google Scholar]
  • 17.Petereit HF, Nolden S, Schoppe S, Bamborschke S, Pukrop R, Heiss WD. Low interferon gamma producers are better treatment responders: a two-year follow-up of interferon beta-treated multiple sclerosis patients. Mult Scier. 2002;8:492–494. doi: 10.1191/1352458502ms853oa. [DOI] [PubMed] [Google Scholar]
  • 18.Killestein J, Hintzen RQ, Uitdehaag BM, et al. Baseline T cell reactivity in multiple sclerosis is correlated to efficacy of interferon-beta. J Neuroimmunol. 2002;133:217–224. doi: 10.1016/S0165-5728(02)00373-9. [DOI] [PubMed] [Google Scholar]
  • 19.Bielekova B, Martin R. Development of biomarkers in multiple sclerosis. Brain. 2004;127:1463–1478. doi: 10.1093/brain/awh176. [DOI] [PubMed] [Google Scholar]
  • 20.Wandinger KP, Lunemann JD, Wengert O, et al. TNF-related apoptosis inducing ligand (TRAIL) as a potential response marker for interferon-beta treatment in multiple sclerosis. Lancet. 2003;361:2036–2043. doi: 10.1016/S0140-6736(03)13641-0. [DOI] [PubMed] [Google Scholar]
  • 21.Alam J, Goelz S, Rioux P, et al. Comparative pharmacokinetics and pharmacodynamics of two recombinant human interferon beta-1a (IFNβ-1a) products administered intramuscularly in healthy male and female volunteers. Pharm Res. 1997;14:546–549. doi: 10.1023/A:1012128406432. [DOI] [PubMed] [Google Scholar]
  • 22.Siddiqui MA, Wellington K. Intramuscular interferon-beta-1a: in patients at high risk of developing clinically definite multiple sclerosis. CNS Drugs. 2005;19:55–61. doi: 10.2165/00023210-200519010-00005. [DOI] [PubMed] [Google Scholar]
  • 23.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. 1993;43:655–661. doi: 10.1212/wnl.43.4.655. [DOI] [PubMed] [Google Scholar]
  • 24.IFNB Multiple Sclerosis Study Group. 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. 1995;45:1277–1285. [PubMed] [Google Scholar]
  • 25.Jacobs LD, Cookfair DL, Rudick RA, Multiple Sclerosis Collaborative Research Group (MSCRG) et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann Neurol. 1996;39:285–294. doi: 10.1002/ana.410390304. [DOI] [PubMed] [Google Scholar]
  • 26.PRISMS (Prevention of Relapses and Disability by Interferon Beta-1a Subcutaneously in Multiple Sclerosis) Study Group Randomised double-blind placebo-controlled study of interferon beta-la in relapsing/remitting multiple sclerosis. Lancet. 1998;352:1498–1504. doi: 10.1016/S0140-6736(98)03334-0. [DOI] [PubMed] [Google Scholar]
  • 27.PRISMS Study Group; University of British Columbia MS/MRI Analysis Group PRISMS-4: long-term efficacy of interferon-beta-1a in relapsing MS. Neurology. 2001;56:1628–1636. doi: 10.1212/wnl.56.12.1628. [DOI] [PubMed] [Google Scholar]
  • 28.Schwid SR, Bever CT. The cost of delaying treatment in multiple sclerosis: what is lost is not regained. Neurology. 2001;56:1620–1620. doi: 10.1212/wnl.56.12.1620. [DOI] [PubMed] [Google Scholar]
  • 29.McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50:121–127. doi: 10.1002/ana.1032. [DOI] [PubMed] [Google Scholar]
  • 30.Jacobs LD, Beck RW, Simon JH, CHAMPS Study Group et al. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. N Engl J Med. 2000;343:898–904. doi: 10.1056/NEJM200009283431301. [DOI] [PubMed] [Google Scholar]
  • 31.Kinkel RP, Kollman C, O’Connor P, et al. IM interferon beta-1a delays definite multiple sclerosis 5 years after a first demyelinating event. Neurology. 2006;66:678–684. doi: 10.1212/01.wnl.0000200778.65597.ae. [DOI] [PubMed] [Google Scholar]
  • 32.Comi G, Filippi M, Barkhof F, et al. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet. 2001;357:1576–1582. doi: 10.1016/S0140-6736(00)04725-5. [DOI] [PubMed] [Google Scholar]
  • 33.Filippi M, Rovaris M, Inglese M, 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. 2004;364:1489–1496. doi: 10.1016/S0140-6736(04)17271-1. [DOI] [PubMed] [Google Scholar]
  • 34.Kappos L, Polman CH, Freedman MS, et al. Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology. 2006;67:1242–1249. doi: 10.1212/01.wnl.0000237641.33768.8d. [DOI] [PubMed] [Google Scholar]
  • 35.Lublin FD, Reingold SC, National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis Defining the clinical course of multiple sclerosis: results of an international survey. Neurology. 1996;46:907–911. doi: 10.1212/wnl.46.4.907. [DOI] [PubMed] [Google Scholar]
  • 36.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. 1998;352:1491–1497. doi: 10.1016/S0140-6736(98)10039-9. [DOI] [PubMed] [Google Scholar]
  • 37.Panitch H, Miller A, Paty D, Weinshenker B. Interferon beta-1b in secondary progressive MS: Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study. Neurology. 2004;63:1788–1795. doi: 10.1212/01.wnl.0000146958.77317.3e. [DOI] [PubMed] [Google Scholar]
  • 38.Kappos L, Weinshenker B, Pozzilli C, European (EU-SPMS) Interferon beta-1b in Secondary Progressive Multiple Sclerosis Trial Steering Committee and Independent Advisory Board. North American (NA-SPMS) Interferon beta-1b in Secondary Progressive Multiple Sclerosis Trial Steering Committee and Independent Advisory Board et al. Interferon beta-1b in secondary progressive MS: a combined analysis of the two trials. Neurology. 2004;63:1779–1787. doi: 10.1212/01.wnl.0000145561.08973.4f. [DOI] [PubMed] [Google Scholar]
  • 39.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. 2001;56:1496–1504. doi: 10.1212/wnl.56.11.1496. [DOI] [PubMed] [Google Scholar]
  • 40.Li DK, Zhao GJ, Paty DW, University of British Columbia MS/ MRI Analysis Research Group. SPECTRIMS Study Group Randomized controlled trial of interferon-beta-1a in secondary progressive MS: MRI results. Neurology. 2001;56:1505–1513. doi: 10.1212/wnl.56.11.1505. [DOI] [PubMed] [Google Scholar]
  • 41.Andersen O, Elovaara I, Färkkilä M, et al. Multicentre, randomised, double blind, placebo controlled, phase III study of weekly, low dose, subcutaneous interferon beta-1a in secondary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry. 2004;75:706–710. doi: 10.1136/jnnp.2003.010090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Cohen JA, Cutter GR, Fischer JS, IMPACT investigators et al. Benefit of interferon beta-1a on MSFC progression in secondary progressive MS. Neurology. 2002;59:679–687. doi: 10.1212/wnl.59.5.679. [DOI] [PubMed] [Google Scholar]
  • 43.Cohen JA, Cutter GR, Fischer JS, et al. Use of the multiple sclerosis functional composite as an outcome measure in a phase 3 clinical trial. Arch Neurol. 2001;58:961–967. doi: 10.1001/archneur.58.6.961. [DOI] [PubMed] [Google Scholar]
  • 44.Leary SM, Miller DH, Stevenson VL, Brex PA, Chard DT, Thompson AJ. Interferon beta-1a in primary progressive MS: an exploratory, randomized, controlled trial. Neurology. 2003;60:44–51. doi: 10.1212/wnl.60.1.44. [DOI] [PubMed] [Google Scholar]
  • 45.Banwell B, Reder AT, Krupp L, et al. Safety and tolerability of interferon beta-lb in pediatric multiple sclerosis. Neurology. 2006;66:472–476. doi: 10.1212/01.wnl.0000198257.52512.1a. [DOI] [PubMed] [Google Scholar]
  • 46.Waubant E, Hietpas J, Stewart T, et al. Interferon beta-1a in children with multiple sclerosis is well tolerated. Neuropediatrics. 2001;32:211–213. doi: 10.1055/s-2001-17370. [DOI] [PubMed] [Google Scholar]
  • 47.Mikaeloff Y, Moreau T, Debouverie M, et al. Interferon-beta treatment in patients with childhood-onset multiple sclerosis. J Pediatr. 2001;139:443–446. doi: 10.1067/mpd.2001.116610. [DOI] [PubMed] [Google Scholar]
  • 48.Ghezzi A, Ruggieri M, Trojano M, et al. Italian studies on early-onset multiple sclerosis: the present and the future. Neurol Sci. 2004;25(Suppl 4):S346–S349. doi: 10.1007/s10072-004-0346-9. [DOI] [PubMed] [Google Scholar]
  • 49.Pohl D, Rostasy K, Gartner J, Hanefeld F. Treatment of early onset multiple sclerosis with subcutaneous interferon beta-1a. Neurology. 2005;64:888–890. doi: 10.1212/01.WNL.0000153570.33845.6A. [DOI] [PubMed] [Google Scholar]
  • 50.Tenembaum SN, Segura MJ. Interferon beta-1a treatment in childhood and juvenile-onset multiple sclerosis. Neurology. 2006;67:511–513. doi: 10.1212/01.wnl.0000231137.24467.aa. [DOI] [PubMed] [Google Scholar]
  • 51.Pohl D, Waubant E, Banwell B, et al. Treatment of pediatric multiple sclerosis and variants. Neurology. 2007;68:S54–S65. doi: 10.1212/01.wnl.0000259407.40023.ab. [DOI] [PubMed] [Google Scholar]
  • 52.Lucchinetti CF, Mandler RN, McGavem D, et al. A role for humoral mechanisms in the pathogenesis of Devic’s neuromyelitis optica. Brain. 2002;125:1450–1461. doi: 10.1093/brain/awf151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.Papeix C, Vidal JS, de Seze J, et al. Immunosuppressive therapy is more effective than interferon in neuromyelitis optica. Mult Scler. 2007;13:256–259. doi: 10.1177/1352458506070732. [DOI] [PubMed] [Google Scholar]
  • 54.Warabi Y, Matsumoto Y, Hayashi H. Interferon beta-1b exacerbates multiple sclerosis with severe optic nerve and spinal cord demyelination. J Neurol Sci. 2007;252:57–61. doi: 10.1016/j.jns.2006.10.008. [DOI] [PubMed] [Google Scholar]
  • 55.Biogen Idec . Product information: Avonex®, interferon beta-1a. Cambridge, MA: Biogen Idee; 2007. [Google Scholar]
  • 56.Serono . Product information: Rebif®, interferon beta-1a. Geneva: Serono; 2007. [Google Scholar]
  • 57.Berlex Laboratories . Product information: Betaseron®, interferon beta-1b. Montville, NJ: Berlex Laboratories; 2007. [Google Scholar]
  • 58.Bayas A, Rieckmann P. Managing the adverse effects of interferon-beta therapy in multiple sclerosis. Drug Saf. 2000;22:149–159. doi: 10.2165/00002018-200022020-00006. [DOI] [PubMed] [Google Scholar]
  • 59.Frohman EM, Brannon K, Alexander S, et al. Disease modifying agent related skin reactions in multiple sclerosis: prevention, assessment, and management. Mult Scler. 2004;10:302–307. doi: 10.1191/1352458504ms1002oa. [DOI] [PubMed] [Google Scholar]
  • 60.Tremlett H, Oger J. Hepatic injury, liver monitoring and the beta-interferons for multiple sclerosis. J Neurol. 2004;251:1297–1303. doi: 10.1007/s00415-004-0619-5. [DOI] [PubMed] [Google Scholar]
  • 61.Tremlett HL, Yoshida EM, Oger J. Liver injury associated with the beta-interferons for MS: a comparison between the three products. Neurology. 2004;62:628–631. doi: 10.1212/wnl.62.4.628. [DOI] [PubMed] [Google Scholar]
  • 62.Durelli L, Verdun E, Barbero P, Independent Comparison of Interferon (INCOMIN) Trial Study Group 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. 2002;359:1453–1460. doi: 10.1016/S0140-6736(02)08430-1. [DOI] [PubMed] [Google Scholar]
  • 63.Noseworthy JH, Ebers GC, Vandervoort MK, Farquhar RE, Yetisir E, Roberts R. The impact of blinding on the results of a randomized, placebo-controlled multiple sclerosis clinical trial. Neurology. 1994;44:16–20. doi: 10.1212/wnl.44.1.16. [DOI] [PubMed] [Google Scholar]
  • 64.Rask C. Comparative study of Rebif to Avonex and orphan exclusivity. Rockville, MD: U.S. Department of Health and Human Services; 2002. [Google Scholar]
  • 65.Schwid SR, Thorpe J, Sharief M, EVIDENCE (Evidence of Interferon Dose-Response: European North American Comparative Efficacy) Study Group. University of British Columbia MS/ MRI Research Group et al. Enhanced benefit of increasing interferon beta-1a dose and frequency in relapsing multiple sclerosis: the EVIDENCE study. Arch Neurol. 2005;62:785–792. doi: 10.1001/archneur.62.5.785. [DOI] [PubMed] [Google Scholar]
  • 66.Clanet M, Radue EW, Kappos L, et al. European IFNbeta-1a (Avonex) Dose-Comparison Study Investigators. A randomized, double-blind, dose-comparison study of weekly interferon beta-1a in relapsing MS. Neurology. 2002;59:1507–1517. doi: 10.1212/01.wnl.0000032256.35561.d6. [DOI] [PubMed] [Google Scholar]
  • 67.Bertolotto A, Gilli F, Sala A, et al. Persistent neutralizing antibodies abolish the interferon beta bioavailability in MS patients. Neurology. 2003;60:634–639. doi: 10.1001/archneur.60.4.634. [DOI] [PubMed] [Google Scholar]
  • 68.Rudick RA, Simonian NA, Alam JA, Multiple Sclerosis Collaborative Research Group (MSCRG) et al. Incidence and significance of neutralizing antibodies to interferon beta-1a in multiple sclerosis. Neurology. 1998;50:1266–1272. doi: 10.1212/wnl.50.5.1266. [DOI] [PubMed] [Google Scholar]
  • 69.Polman CH, Kappos L, Petkau J, Thompson A. Neutralising antibodies to interferon beta during the treatment of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2003;74:1162–1162. doi: 10.1136/jnnp.74.8.1162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70.Sorensen PS, Ross C, Clemmesen KM, et al. Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis. Lancet. 2003;362:1184–1191. doi: 10.1016/S0140-6736(03)14541-2. [DOI] [PubMed] [Google Scholar]
  • 71.Francis GS, Rice GP, Alsop JC, PRISMS Study Group Interferon beta-1a in MS: results following development of neutralizing antibodies in PRISMS. Neurology. 2005;65:48–55. doi: 10.1212/01.wnl.0000171748.48188.5b. [DOI] [PubMed] [Google Scholar]
  • 72.Panitch H, Goodin DS, Francis G, EVIDENCE Study Group et al. Evidence of interferon dose-response: European North American Comparative Efficacy; University of British Columbia MS/MRI Research Group. Randomized, comparative study of interferon beta-1a treatment regimens in MS: the EVIDENCE trial. Neurology. 2002;59:1496–1506. doi: 10.1212/01.wnl.0000034080.43681.da. [DOI] [PubMed] [Google Scholar]
  • 73.Perini P, Facchinetti A, Bulian P, et al. Interferon-beta (INF-β) antibodies in interferon-β1a- and interferon-β1b-treated multiple sclerosis patients: prevalence, kinetics, cross-reactivity, and factors enhancing interferon-beta immunogenicity in vivo. Eur Cytokine Netw. 2001;12:56–61. [PubMed] [Google Scholar]
  • 74.Goodin DS, Frohman EM, Hurwitz B, 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. 2007;68:977–984. doi: 10.1212/01.wnl.0000258545.73854.cf. [DOI] [PubMed] [Google Scholar]
  • 75.Fisher E, Rudick RA, Cutter G, et al. Relationship between brain atrophy and disability: an 8-year follow-up study of multiple sclerosis patients. Mult Scler. 2000;6:373–377. doi: 10.1177/135245850000600602. [DOI] [PubMed] [Google Scholar]
  • 76.Rudick RA. Impact of disease-modifying therapies on brain and spinal cord atrophy in multiple sclerosis [Review] J Neuroimaging. 2004;14:54S–64S. doi: 10.1111/j.1552-6569.2004.tb00279.x. [DOI] [PubMed] [Google Scholar]
  • 77.Rudick RA, Fisher E, Lee JC, et al. Multiple Sclerosis Collaborative Research Group. Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Neurology. 1999;53:1698–1704. doi: 10.1212/wnl.53.8.1698. [DOI] [PubMed] [Google Scholar]
  • 78.Hardmeier M, Wagenpfeil S, Freitag P, et al. Rate of brain atrophy in relapsing MS decreases during treatment with IFNβ-1a. Neurology. 2005;64:236–240. doi: 10.1212/01.WNL.0000149516.30155.B8. [DOI] [PubMed] [Google Scholar]
  • 79.Jones CK, Riddehough A, Li DKB, et al. MRI cerebral atrophy in relapsing-remitting MS: results from the PRISMS trial [Abstract] Neurology. 2001;56(suppl 3):A379–A379. [Google Scholar]
  • 80.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;8:119–123. doi: 10.1191/1352458502ms788oa. [DOI] [PubMed] [Google Scholar]
  • 81.Frank JA, Richert N, Bash C, et al. Interferon-beta-1b slows progression of atrophy in RRMS: three-year follow-up in NAb− and NAb+ patients. Neurology. 2004;62:719–725. doi: 10.1212/01.wnl.0000113765.75855.19. [DOI] [PubMed] [Google Scholar]
  • 82.Molyneux PD, Kappos L, Polman C, European Study Group on Interferon Beta-1b in Secondary Progressive Multiple Sclerosis et al. The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis. Brain. 2000;123:2256–2263. doi: 10.1093/brain/123.11.2256. [DOI] [PubMed] [Google Scholar]
  • 83.Yong VW, Chabot S, Stuve O, Williams G. Interferon beta in the treatment of multiple sclerosis: mechanisms of action. Neurology. 1998;51:682–689. doi: 10.1212/wnl.51.3.682. [DOI] [PubMed] [Google Scholar]
  • 84.Biemacki K, Antel JP, Blain M, Narayanan S, Arnold DL, Prat A. Interferon beta promotes nerve growth factor secretion early in the course of multiple sclerosis. Arch Neurol. 2005;62:563–568. doi: 10.1001/archneur.62.4.563. [DOI] [PubMed] [Google Scholar]
  • 85.Bermel RA, Puli SR, Rudick RA, et al. Prediction of longitudinal brain atrophy in multiple sclerosis by gray matter magnetic resonance imaging T2 hypointensity. Arch Neurol. 2005;62:1371–1376. doi: 10.1001/archneur.62.9.1371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 86.Rudick RA, Cutter GR, Baier M, et al. Estimating long-term effects of disease-modifying drug therapy in multiple sclerosis patients. Mult Scler. 2005;11:626–634. doi: 10.1191/1352458505ms1203oa. [DOI] [PubMed] [Google Scholar]
  • 87.Kappos L, Traboulsee A, Constantinescu C, et al. Long-term subcutaneous interferon beta-1a therapy in patients with relapsing-remitting MS. Neurology. 2006;67:944–953. doi: 10.1212/01.wnl.0000237994.95410.ce. [DOI] [PubMed] [Google Scholar]
  • 88.Ebers G, Traboulsee A, Li D, et al. Final results from the interferon beta-1b 16-year long-term follow-up study. Mult Scler. 2006;12:S228–S228. [Google Scholar]
  • 89.Trojano M, Pellegrini F, Fuiani A, et al. New natural history of interferon-beta-treated relapsing multiple sclerosis. Ann Neurol. 2007;61:300–306. doi: 10.1002/ana.21102. [DOI] [PubMed] [Google Scholar]
  • 90.Bell C, Graham J, Earnshaw S, Oleen-Burkey M, Castelli-Haley J, Johnson K. Cost-effectiveness of four immunomodulatory therapies for relapsing-remitting multiple sclerosis: a Markov model based on long-term clinical data. J Manag Care Pharm. 2007;13:245–261. doi: 10.18553/jmcp.2007.13.3.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 91.Kobelt G, Jönsson L, Fredrikson S. Cost-utility of interferon betalb in the treatment of patients with active relapsing-remitting or secondary progressive multiple sclerosis. Eur J Health Econ. 2003;4:50–59. doi: 10.1007/s10198-002-0163-0. [DOI] [PubMed] [Google Scholar]
  • 92.Phillips CJ. The cost of multiple sclerosis and the cost effectiveness of disease-modifying agents in its treatment. CNS Drugs. 2004;18:561–574. doi: 10.2165/00023210-200418090-00002. [DOI] [PubMed] [Google Scholar]
  • 93.Coyle PK, Johnson KP. Relapses matter: the costs & consequences of multiple sclerosis relapses. J Neurol Sci. 2007;256(Suppl 1):S1–S4. doi: 10.1016/j.jns.2007.01.058. [DOI] [PubMed] [Google Scholar]
  • 94.Chilcott J, McCabe C, Tappenden P, et al. Cost Effectiveness of Multiple Sclerosis Therapies Study Group. Modelling the cost effectiveness of interferon beta and glatiramer acetate in the management of multiple sclerosis. Commentary: evaluating disease modifying treatments in multiple sclerosis. BMJ. 2003;326:522–522. doi: 10.1136/bmj.326.7388.522. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Neurotherapeutics are provided here courtesy of Elsevier

RESOURCES