Intervention Review

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Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis

  1. Graziella Filippini1,*,
  2. Cinzia Del Giovane2,
  3. Laura Vacchi3,
  4. Roberto D'Amico2,
  5. Carlo Di Pietrantonj4,
  6. Deirdre Beecher5,
  7. Georgia Salanti6

Editorial Group: Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group

Published Online: 6 JUN 2013

Assessed as up-to-date: 10 FEB 2012

DOI: 10.1002/14651858.CD008933.pub2

How to Cite

Filippini G, Del Giovane C, Vacchi L, D'Amico R, Di Pietrantonj C, Beecher D, Salanti G. Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD008933. DOI: 10.1002/14651858.CD008933.pub2.

Author Information

  1. 1

    Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, Neuroepidemiology Unit, Milano, Italy

  2. 2

    University of Modena and Reggio Emilia, Statistics Unit, Department of Clinical and Diagnostic Medicine and Public Health, Modena, Italy

  3. 3

    Scientific Institute and University Ospedale San Raffaele, Institute of Experimental Neurology (INSPE), Milano, Italy

  4. 4

    Azienda Sanitaria Locale ASL AL, Servizio Regionale di Riferimento per l'Epidemiologia, SSEpi-SeREMI - Cochrane Vaccines Field, Alessandria, Piemonte, Italy

  5. 5

    London School of Hygiene & Tropical Medicine, Cochrane Injuries Group, London, UK

  6. 6

    University of Ioannina School of Medicine, Department of Hygiene and Epidemiology, Ioannina, Greece

*Graziella Filippini, Neuroepidemiology Unit, Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, via Celoria, 11, Milano, 20133, Italy. gfilippini@istituto-besta.it.

Publication History

  1. Publication Status: New
  2. Published Online: 6 JUN 2013

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References

References to studies included in this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
Achiron 1998 {published data only}
  • Achiron A, Gabbay U, Gilad R, Hassin B, Barak Y, Gornish M, et al. Intravenous immunoglobulin treatment in multiple sclerosis. Effect on relapses. Neurology 1998;50(2):398-402.
AFFIRM 2006 {published data only}
  • Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. The New England Journal of Medicine 2006;354(9):899-910.
Andersen 2004 {published data only}
  • Andersen O, Elovaara I, Farkkila M, Hansen HJ, Mellgren SI, Myhr KM, et al. Multicentre, randomised, double blind, placebo controlled, phase III study of weekly, low dose, subcutaneous interferon beta-1a in secondary progressive multiple sclerosis. Journal of Neurology, Neurosurgery, and Psychiatry 2004;75(5):706-10. [PUBMED: 15090564]
BEYOND 2009 {published data only}
  • O'Connor P, Filippi M, Arnason B, Comi G, Cook S, Goodin D, et al. 250 microg or 500 microg interferon beta-1b versus 20 mg glatiramer acetate in relapsing-remitting multiple sclerosis: a prospective, randomised, multicentre study. Lancet Neurology 2009;8(10):889-97.
Bornstein 1987 {published data only}
  • Bornstein MB, Miller A, Slagle, S, Weitzman M, Crystal, et al. A pilot trial of Cop 1 in exacerbating-remitting multiple sclerosis. The New England Journal of Medicine 1987; Vol. 317, issue 7:408-14.
Bornstein 1991 {published data only}
  • Bornstein MB, Miller A, Slagle S, Weitzman M, Drexler E, Keilson Metal. A placebo-controlled, double-blind, randomised, two-center, pilot trial of Cop 1 in chronic progressive multiple sclerosis. Neurology 1991;41:533-9. [: DOI]
BPSM 1995 {published data only}
British and Dutch 1988 {published data only}
  • The British, Dutch MSATG. Double-masked trial of azathioprine in multiple sclerosis. Lancet 1988; Vol. 2, issue 8604:179-83.
CCMSSG 1991 {published data only}
  • CCMSSG. The Canadian cooperative trial of cyclophosphamide and plasma exchange in progressive multiple sclerosis. Lancet 1991;337(8739):441-6.
Comi 2001 {published data only}
  • Comi G, Filippi M, Wolinsky JS. 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. Annals of Neurology 2001;49(3):290-7. [PUBMED: 11261502]
Edan 1997 {published data only}
  • Edan G, Miller D, Clanet M, Confavreux C, Lyon-Caen O, Lubetzki C, et al. Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria. Journal of Neurology, Neurosurgery, and Psychiatry 1997;62(2):112-8. [: DOI]
Ellison 1989 {published data only}
  • Ellison G, Myers L, Mickey M, Graves M, Tourtellotte W, Syndulko K, et al. A placebo-controlled, randomized, double-masked, variable dosage, clinical trial of azathioprine with and without methylprednisolone in multiple sclerosis. Neurology 1989;39(8):1018-26.
Etemadifar 2006 {published data only}
European Study Group 1998 {published data only}
  • European Study Group. Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. European Study Group on interferon beta-1b in secondary progressive MS. Lancet 1998;352(9139):1491-7. [PUBMED: 9820296]
EVIDENCE 2007 {published data only}
  • Schwid S, Panitch H. Full results of the Evidence of Interferon Dose-Response-European North American Comparative Efficacy (EVIDENCE) study: a multicenter, randomized, assessor-blinded comparison of low-dose weekly versus high-dose, high-frequency interferon beta-1a for relapsing multiple sclerosis. Clinical Therapeutics 2007;29(9):2031-48. [PUBMED: 18035202]
Fazekas 1997 {published data only}
  • Fazekas F, Deisenhammer F, Strasser-Fuchs S, Nahler G, Mamoli B. Randomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Lancet 1997;349(9052):589-93.
Fazekas 2008 {published data only}
  • Fazekas F, Lublin F, Li D, Freedman M, Hartung H, Rieckmann P, et al. Intravenous immunoglobulin in relapsing-remitting multiple sclerosis: a dose-finding trial. Neurology 2008;71(4):265-71.
Ghezzi 1989 {published data only}
  • Ghezzi A, Di Falco M, Locatelli C. In: Consette RE, Delmotte P editor(s). Clinical controlled randomized trial of azathioprine in multiple sclerosis. Elsevier, 1989.
Goodkin 1991 {published data only}
  • Goodkin D, Bailly R, Teetzen M, Hertsgaard D, Beatty W. The efficacy of azathioprine in relapsing-remitting multiple sclerosis. Neurology 1991;41:20-5. [: DOI]
Goodkin 1995 {published data only}
  • Goodkin D, Rudick R, VanderBrug Medendorp S, Daughtry M, Schwetz K, Fischer J, et al. Low-dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis. Annals of Neurology 1995;37(1):30-40. [PUBMED: 7818255]
Hartung 2002 {published data only}
  • Hartung H, Gonsette R, Konig N, Kwiecinski H, Guseo A, Morrissey S, et al. Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet 2002;360(9350):2018-25. [PUBMED: 12504397]
Hommes 2004 {published data only}
  • Hommes O, Sorensen P, Fazekas F, Enriquez M, Koelmel H, Fernandez O, et al. Intravenous immunoglobulin in secondary progressive multiple sclerosis: randomised placebo-controlled trial. Lancet 2004;364(9440):1149-56.
IFNB MS Group 1993 {published data only}
  • IFNB MSG. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. The IFNB Multiple Sclerosis Study Group. Neurology 1993;43(4):655-61. [PUBMED: 8469318]
IMPACT 2002 {published data only}
  • Cohen J, Cutter G, Fischer J, Goodman A, Heidenreich F, Kooijmans M, et al. Benefit of interferon beta-1a on MSFC progression in secondary progressive MS. Neurology 2002;59(5):679-87. [PUBMED: 12221157]
INCOMIN 2002 {published data only}
  • Durelli L, Verdun E, Barbero P, Bergui M, Versino E, Ghezzi A, et al. Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis: results of a 2-year prospective randomised multicentre study (INCOMIN). Lancet 2002;359:1453-60.
Johnson 1995 {published data only}
  • Johnson K, Brooks B, Cohen J, Ford C, Goldstein J, Lisak R, 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. The Copolymer 1 Multiple Sclerosis Study Group. Neurology 1995;45(7):1268-76. [PUBMED: 7617181]
Knobler 1993 {published data only}
  • Knobler R, Greenstein J, Johnson K, Lublin F, Panitch H, Conway K, et al. Systemic recombinant human interferon-beta treatment of relapsing-remitting multiple sclerosis: pilot study analysis and six-year follow-up. Journal of Interferon Research 1993;13:333-40. [PUBMED: 8301153]
Koch-Henriksen 2006 {published data only}
  • Koch-Henriksen N, Sørensen P, Christensen T, Frederiksen J, Ravnborg M, Jensen K, et al. A randomised study of two interferon-beta treatments in relapsing-remitting multiple sclerosis. Neurology 2006;66(7):1056-60.
Leary 2003 {published data only}
  • Leary S, Miller D, Stevenson V, Brex P, Chard D, Thompson A. Interferon beta-1a in primary progressive MS: an exploratory, randomized, controlled trial. Neurology 2003;60(1):44-51. [PUBMED: 12525716]
Lewanska 2002 {published data only}
Likosky 1991 {published data only}
  • Likosky W, Fireman B, Elmore R, Eno G, Gale K, Goode G, et al. Intense immunosuppression in chronic progressive multiple sclerosis: the Kaiser study. Journal of Neurology, Neurosurgery, and Psychiatry 1991; Vol. 54, issue 12:1055-60.
Milanese 1993 {published data only}
Millefiorini 1997 {published data only}
  • Millefiorini E, Gasperini C, Pozzilli C, D'Andrea F, Bastianello S, Trojano M, et al. Randomized placebo-controlled trial of mitoxantrone in relapsing-remitting multiple sclerosis: 24-month clinical and MRI outcome. Journal of Neurology 1997;244(3):153-9. [PUBMED: 9050955]
Miller 1961 {published data only}
  • Miller H, Newell D, Ridley A. Multiple sclerosis. Trials of maintenance treatment with prednisolone and soluble aspirin. Lancet 1961; Vol. 1, issue 7169:127-9.
Montalban 2009 {published data only}
  • Montalban X, Sastre-Garriga J, Tintore M, Brieva L, Aymerich F, Rio J, et al. A single-center, randomized, double-blind, placebo-controlled study of interferon beta-1b on primary progressive and transitional multiple sclerosis. Multiple Sclerosis 2009;15(10):1195-205. [PUBMED: 19797261]
MSCRG 1996 {published data only}
  • Jacobs L, Cookfair D, Rudick R, Herndon R, Richert J, Salazar A, et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Annals of Neurology 1996;39:285-94.
NASP 2004 {published data only}
  • Panitch H, Miller A, Paty D, Weinshenker B. Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study. Neurology 2004;63(10):1788-95. [PUBMED: 15557491]
OWIMS 1999 {published data only}
  • OWIMS. Evidence of interferon beta-1a dose response in relapsing-remitting MS: the OWIMS Study. The Once Weekly Interferon for MS Study Group. Neurology 1999;53(4):679-86. [PUBMED: 10489026]
Pohlau 2007 {published data only}
  • Pohlau D, Przuntek H, Sailer M, Bethke F, Koehler J, Konig N, et al. Intravenous immunoglobulin in primary and secondary chronic progressive multiple sclerosis: a randomized placebo controlled multicentre study. Multiple Sclerosis 2007;13(9):1107-17. [PUBMED: 17623736]
PRISMS 1998 {published data only}
  • PRISMS. Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet 1998;352(9139):1498-504. [PUBMED: 9820297]
REGARD 2008 {published data only}
  • Mikol D, Barkhof F, Chang P, Coyle P, Jeffery D, Schwid S, et al. Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicentre, randomised, parallel, open-label trial. Lancet Neurology 2008;7(10):903-14.
SENTINEL 2006 {published data only}
  • Rudick R, Stuart W Calabresi P, Confavreux C, Galetta S, Radue E, et al. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. The New England Journal of Medicine 2006;354(9):911-23.
SPECTRIMS 2001 {published data only}
  • SPECTRIMS. Randomized controlled trial of interferon- beta-1a in secondary progressive MS: Clinical results. Neurology 2001;56(11):1496-504. [PUBMED: 11402106]
Wolinsky 2007 {published data only}

References to studies excluded from this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
Arnason 1999 {published data only}
  • Arnason, BGW, Jacobs G, Hanlon M, Harding B, Noronha ABC, Auty A, et al. TNF neutralization in MS: Results of a randomized, placebo-controlled multicenter study. Neurology 1999;53(3):457-65.
Barkhof 2003 {published data only}
Baum 2006 {published data only}
  • Baum K, Mannitol Formulation Study Group. Safety and tolerability of a 'refrigeration-free' formulation of interferon beta-1b--results of a double-blind, multicentre, comparative study in patients with relapsing-remitting or secondary progressive multiple sclerosis. The Journal of International Medical Research 2006;34(1):1-12.
BENEFIT 2006 {published data only}
  • Kappos L, Polman C, Freedman M, Edan G, Hartung H, Miller D, et al. Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology 2006;67(7):1242-9.
Boiko 2001 {published data only}
  • Boiko A, Skurkovich S, Buglak A, Alekseeva, T, Smirnova N, Skurkovich B, et al. Randomized, placebo-controlled trial comparing short course of anti-IFN? And anti-TNFa showed only anti-IFN? Effective in secondary progressive MS. Journal of Neurosurgery 2001;187 Suppl 1:S456.
Burton 2009 {published data only}
CHAMPS 2000 {published data only}
  • Jacobs L, Beck R, Simon J, Kinkel R, Brownscheidle C, Murray T, et al. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. The New England Journal of Medicine 2000;343(13):898-904. [PUBMED: 11006365]
Christodoulou 2006 {published data only}
  • Christodoulou C, Melville P, Scherl WF, MacAllister WS, Elkins LE, Krupp LB. Effects of donepezil on memory and cognition in multiple sclerosis. Journal of the Neurological Sciences 2006;245(1-2):127-36.
Clanet 2002 {published data only}
  • Clanet M, Radue E, Kappos L, Hartung H, Hohlfeld R, Sandberg-Wollheim M, et al. A randomized, double-blind, dose-comparison study of weekly interferon beta-1a in relapsing MS. Neurology 2002;59(10):1507-17. [PUBMED: 12451189]
Durelli 1994 {published data only}
  • Durelli L, Bongioanni M, Cavallo R, Ferrero B, Ferri R, Ferrio M, 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;44(3 (Pt 1)):406-13.
ETOMS 2001 {published data only}
  • Comi G, Filippi M, Barkhof F, Durelli L, Edan G, Fernández O, et al. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 2001;357(9268):1576-82.
Fernandez 2002 {published data only}
  • Fernandez O, Guerrero M, Mayorga C, Munoz L, Lean A, Luque G, et al. Combination therapy with interferon beta-1b and azathioprine in secondary progressive multiple sclerosis. A two-year pilot study. Journal of Neurology 2002;249(8):1058-62.
Filippi 2004 {published data only}
  • Filippi M, Rovaris M, Inglese M, Barkhof F, De Stefano N, Smith S, et al. Interferon beta-1a for brain tissue loss in patients at presentation with syndromes suggestive of multiple sclerosis: a randomised, double blind, placebo-controlled trial. Lancet 2004;364(9444):1489-96.
Filippi 2006 {published data only}
  • Filippi M, Wolinsky J, Comi G. Effects of oral glatiramer acetate on clinical and MRI-monitored disease activity in patients with relapsing multiple sclerosis: a multicentre, double-blind, randomised, placebo-controlled study. Lancet Neurology 2006;5:213-20.
GLANCE 2009 {published data only}
  • Goodman A, Rossman H, Bar-Or A, Miller A, Miller D, Schmierer K, et al. GLANCE: Results of a phase 2, randomized, double-blind, placebo-controlled study. Neurology 2009;72:806-12.
Goodkin 2000 {published data only}
  • Goodkin DE, Shulman M, Winkelhake J, Waubant E, Andersson P, Stewart T, et al. A phase I trial of solubilized DR2:MBP84-102 (AG284) in multiple sclerosis. Neurology 2000;54(7):1414.
Hauser 1983 {published data only}
  • Hauser S, Dawson D, Lehrich J, Beal M, Kevy S, Propper R, et al. Intensive immunosuppression in progressive multiple sclerosis. A randomized, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange and ACTH [comment in: N Engl J Med 1983;309:239-40; comment in: N Engl J Med 1983;309:241; comment in: Lancet 1991;337:1540-1]. The New England Journal of Medicine 1983;308(4):173-80.
Hoogervorst 2002 {published data only}
Labetouelle 2001 {published data only}
  • Labetouelle M. [About the article: " Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis" by Jacobs LD et al]. Journal Francais of Ophthalmology 2001;24(2):222.
Liu 2010 {published data only}
Myhr 1999 {published data only}
  • Myhr K, Riise T, Green L, Beiske T, Celius E, Edland A, et al. Interferon-alpha2a reduces MRI disease activity in relapsing-remitting multiple sclerosis. Norwegian Study Group on Interferon-alpha in Multiple Sclerosis. Neurology 1999;52(5):1049-56. [MEDLINE: 99200550]
Patti 1999 {published data only}
  • Patti F, L'Episcopo MR, Cataldi ML, Reggio A. Natural interferon-beta treatment of relapsing-remitting and secondary-progressive multiple sclerosis patients. A two-year study. Acta Neurologica Scandinavica 1999;100(5):283-9.
Rio 2007 {published data only}
  • Río J, Tintoré M, Nos C, Téllez N, Galán I, Pelayo R, et al. Interferon beta in secondary progressive multiple sclerosis. Daily clinical practice. Journal of Neurology 2007;254:849–53.
Skurkovich 2001 {published data only}
  • Skurkovich S, Boiko A, Beliaeva I, Buglak A, Alekseeva T, Smirnova N, et al. Randomized study of antibodies to IFN-gamma and TNF-alpha in secondary progressive multiple sclerosis. Multiple Sclerosis 2001;7(5):277-84.
Steultjens 2003 {published data only}
  • Steultjens E, Dekker J, Bouter L, Cardol M, Van den Ende E, van de Nes J. Occupational therapy for multiple sclerosis. Cochrane Database of Systematic Reviews 2003, Issue 3. [DOI: 10.1002/14651858.CD003608; : CD003608]
Tejani 2010 {published data only}
Tubridy 1999 {published data only}
  • Tubridy N, Behan PO, Capildeo R, Chaudhuri A, Forbes R, Hawkins CP, et al. The effect of anti-[alpha]4 integrin antibody on brain lesion activity in MS. Neurology 1999;53(3):466-72.
Van de Wyngaert 2001 {published data only}
  • van de Wyngaert F, Beguin C, D'Hooghe M, Dooms G, Lissoir F, Carton H, et al. A double-blind clinical trial of mitoxantrone versus methylprednisolone in relapsing, secondary progressive multiple sclerosis. Acta Neurologica Belgica 2001;101(4):210-6.
Wender 1988 {published data only}
  • Wender M, Tokarz-Kupczyk E, Mularek O. Early results of the treatment of chronic progressive forms of multiple sclerosis with cyclophosphamide and ACTH [Wczesne wyniki leczenia postaci przewlekle postepujacych stwardnienia rozsianego cyklofosfamidem i ACTH]. Neurologia i Neurochirurgia Polska 1988;22(5):399-403.
Zavalishin 2003 {published data only}
  • Zavalishin IA, Gusev EI, Iakhno NN, Skoromets AA, Ko AN, Demina TL, et al. Results of a multicenter study of Rebif-22 mcg administration in Russia. Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova / Ministerstvo zdravookhraneniia i meditsinskoi promyshlennosti Rossiiskoi Federatsii, Vserossiiskoe obshchestvo nevrologov [i] Vserossiiskoe obshchestvo psikhiatrov 2003;Spec No 2:S73-8.
Zivadinov 2001 {published data only}
  • Zivadinov R, Rudick R, De Masi R, Nasuelli D, Ukmar M, et al. Effects of IV methylprednisolone on brain atrophy in relapsing-remitting MS. Neurology 2001;57(7):1239-47.

Additional references

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
Association of British Neurologists 2005
  • Association of British Neurologists 2005. Guidelines for the Use of Intravenous Immunoglobulin in Neurological Diseases. www.theabn.org/documents/IVIg-Guidelines 2005. [: OTHER]
Bennett 2009
  • Bennett J, Stüve O. Update on inflammation, neurodegeneration, and immunoregulation in multiple sclerosis: therapeutic implications. Clinical Neuropharmacology 2009;32(3):121-32.
Billiau 2004
  • Billiau A, Kieseier B, Hartung H. Biologic role of interferon beta in multiple sclerosis. Journal of Neurology 2004;251 Suppl 2:II10-4.
Birnbaum 2008
Bloomgren 2012
  • Bloomgren G, Richman S, Hotermans C, Subramanyam M, Goelz S, Natarajan A, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. The New England journal of medicine 2012;366(20):1870-80.
Byrnes 2006
  • V Byrnes, N Afdhal, T Challies, PE Greenstein. Drug induced liver injury secondary to interferon-beta (IFN- β) in multiple sclerosis. Annals of Hepatology 2006;5(1):56-9.
Calabresi 1991
  • Calabresi P, Chabner B. Antineoplastic agents. In: Goodman, Gillman's. Hardman JGLimbird LE, Molinoff PB, Ruddon RW, Goodman Gillman A editor(s). Goodman & Gillman's. The Pharmacological Basis of Therapeutics. Eighth. Vol. II, New York: Pergamon Press, 1991:1209-23.
Caldwell 2005
Casetta 2007
Chaimani 2012
Ciccone 2008
Compston 2002
Daumer 2009
Del Giovane 2013
DerSimonian 1986
Ebers 2006
Ebers 2008
Elovaara 2008
  • Elovaara I, Apostolski S, van Doorn P, Gilhus N, Hietaharju A, Honkaniemi J, et al. EFNS guidelines for the use of intravenous immunoglobulin in treatment of neurological diseases: EFNS task force on the use of intravenous immunoglobulin in treatment of neurological diseases. European Journal of Neurology 2008;15(9):893-908.
EMEA 2002
  • European Agency for the Evaluation of Medicinal Products. Committee for Proprietary Medicinal Products European Public Assessment Report (EPAR): Betaferon. London: EMEA 2002.
FDA 1993
  • U.S. Food, Drug Administration. Betaseron Interferon BETA-1B Subcutaneous. Drug Approval Package- Licensing Action 07/23/1993. http://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/103471s0000TOC.cfm.
FDA 1996
  • U.S. Food, Drug Administration. Glatiramer acetate (Copaxone) Product Approval Information Licensing Action 12/20/1996. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory#apphist.
FDA 2000
  • U.S. Food, Drug Administration. Mitoxantrone (Novantrone) Product Approval Information - Licensing Action Approval Date: 1/28/2000. http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/index.cfm?fuseaction=Search.DrugDetails.
FDA 2001
  • U.S. Food, Drug Administration. Interferon 1b (Betaseron) treatment of secondary progressive forms of multiple sclerosis. Clinical review of the June 28, 2000 amendment to supplemental BLA 98-0737 -- STN103471. http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm088275.pdf (accessed 17 Feb 2011).
FDA 2002
  • U.S. Food, Drug Administration. Interferon beta-1a (Rebif) Product Approval Information - Licensing Action Approval Date: 3/7/2002. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm080737.htm.
FDA 2003
  • U.S. Food, Drug Administration. Food and Drug Administration. Interferon beta-1a (AVONEX)Product Approval Information - Licensing Action 5/28/03. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm080469.htm.
FDA 2004
  • U.S. Food, Drug Administration. Tysabri (Natalizumab) Approval Date: 11/23/2004. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/125104s000_Natalizumab.cfm.
FDA 2005
  • U.S. Food, Drug Administration. Mitoxantrone Hydrochloride (marketed as Novantrone and generics) - Healthcare Professional Sheet text version. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm126445.htm (accessed November 2011).
FDA 2011
  • U.S. Food, Drug Administration. COPAXONE® (glatiramer acetate injection) solution for subcutaneous injection. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesbyFDA/WarningLettersandNoticeofViolationLetterstoPharmaceuticalCompanies/UCM296204.pdf (accessed September 2012).
Filippini 2007
  • Filippini G, Ebers G. Multiple sclerosis: critical review of the evidence for each question. In: Candelise L, Hughes R, Liberati A, Uitdehaag BMJ, Warlow C editor(s). Evidence-Based Neurology. Management of neurological disorders. 1st Edition. Blackwell Publishing, 2007:221-33.
Fontoura 2010
Fox 2004
  • Fox E. Mechanism of action of mitoxantrone. Neurology 2004;63(12):S15-8.
Fragoso 2010
  • Fragoso Y, Frota E, Lopes J, Noal J, Giacomo M, Gomes S, et al. Severe depression, suicide attempts, and ideation during the use of interferon beta by patients with multiple sclerosis. Clinical Neuropharmacology 2010;33(6):312-6.
Fragoso 2011
  • Fragoso Y, Paggiaro M, Mastromauro R, da Silva Jacondino G, Wilson H. Literature systematic review on the ophthalmological side effects of interferons. Arquivos Brasileiros de Oftalmologia 2011;74(4):306-10.
Glenny 2005
Goodin 2002
  • Goodin D, Frohman E, Garmany G, Halper J, Likosky W, Lublin F, et al. Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology 2002;58(2):169-78.
Goodman 2009
  • Goodman A, Rossman H, Bar-Or A, Miller A, Miller D, Schmierer K, et al. GLANCE: results of a phase 2, randomized, double-blind, placebo-controlled study. Neurology 2009;72(9):806-12.
Gray 2003
  • Gray O, McDonnell G, Forbes R. Intravenous immunoglobulins for multiple sclerosis. Cochrane Database of Systematic Reviews 2003, Issue Issue 3. Art. No.: CD002936. [DOI: 10.1002/14651858.CD002936]
Gray 2004
Higgins 1996
Higgins 2011
  • Higgins J, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011] . Available from www.cochrane-handbook.org. The Cochrane Collaboration, 2011.
Johnston 2005
  • Johnston A, Gudjonsson J, Sigmundsdottir H, Runar L, Valdimarsson H. The anti-inflammatory action of methotrexate is not mediated by lymphocyte apoptosis, but by the suppression of activation and adhesion molecules. Clinical Immunology 2005;114(2):154-63.
Khoury 2010
  • Khoury S, Healy B, Kivisäkk P, Viglietta V, Egorova S, Guttmann C, et al. A randomized controlled double-masked trial of albuterol add-on therapy in patients with multiple sclerosis. Archives of Neurology 2010;67(9):1055-61.
Kremenchutzky 2006
  • Kremenchutzky M, Rice G, Baskerville J, Wingerchuk D, Ebers G. The natural history of multiple sclerosis: a geographically based study. 9. Observations on the progressive phase of the disease. Brain 2006;129:584-94.
Kurtzke 1983
  • Kurtzke J. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983;33:1444-52.
La Mantia 2007
La Mantia 2010
La Mantia 2012
Lalive 2011
  • Lalive P, Neuhaus O, Benkhoucha M, Burger D, Hohlfeld R, Zamvil S, et al. Glatiramer acetate in the treatment of multiple sclerosis: emerging concepts regarding its mechanism of action. CNS Drugs 2011;25(5):401-14.
Le Page 2011
  • Le Page E, Leray E, Edan G, French Mitoxantrone Safety Group. Long-term safety profile of mitoxantrone in a French cohort of 802 multiple sclerosis patients: a 5-year prospective study. Multiple Sclerosis 2011;17(7):867-75.
Lu 2004
Lu 2006
Lublin 1996
  • Lublin F, Reingold S. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 1996;46:907-11.
Martinelli 2005
McDonald 2001
Milo 2010
Nabavi 2011
  • Nabavi S, Hamzehloo A, Shams J, Morsali D. Reversible therapy-related dysplastic hematopoiesis following beta interferon therapy in multiple sclerosis patients: report of 2 Cases. Iranian Journal of Neurology 2011;10(1-2):32-4.
Nakamura 2008
  • Nakamura Y, Kawachi Y, Furuta J, Otsuka F. Severe local skin reactions to interferon beta-1b in multiple sclerosis-improvement by deep subcutaneous injection. European Journal of Dermatology 2008;18(5):579-82.
Nonchev 2010
  • Nonchev B. Cases of interferon-alpha and interferon-beta-induced thyroiditis. Folia Medica (Plovdiv) 2010;52(3):5-12.
Polman 2005
Poser 1983
Pozzilli 2004
Pucci 2011
Ravnborg 2010
  • Ravnborg M, Sørensen P, Andersson M, Celius E, Jongen P, Elovaara I, et al. Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial. Lancet Neurology 2010;9:672–80.
Rice 2001
  • Rice G, Incorvaia B, Munari L, Ebers G, Polman C, D'Amico R, et al. Interferon in relapsing-remitting multiple sclerosis. Cochrane Database of Systematic Reviews 2001, Issue 4. [DOI: 10.1002/14651858.CD002002]
Rojas 2010
Salanti 2008
Salanti 2009
  • Salanti G, Marinho V, Higgins J. A case study of multiple-treatments meta-analysis demonstrates that covariates should be considered. Journal of Clinical Epidemiology 2009;62:857-64.
Salanti 2011
  • Salanti G, Ades A, Ioannidis J. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. Journal of Clinical Epidemiology 2011;64:163-71.
Schünemann 2011a
  • Schünemann H, Oxman A, Higgins J, Vist G, Glasziou P, Guyatt G. Chapter 11: Presenting results and ‘Summary of findings’ tables. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org, Version 5.0.1 (updated March 2011).
Schünemann 2011b
  • Schünemann H, Oxman A, Vist G, Higgins J, Deeks J, Glasziou P, et al. Chapter 12: Interpreting results and drawing conclusions. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org, Version 5.1.0 (updated March 2011).
Shirani 2012
  • Shirani A, Zhao Y, Karim M, Evans C, Kingwell E, van der Kop M, et al. Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis. JAMA 2012;308(3):247-56. [: OTHER]
Sloka 2005
Smith 2010
  • Smith B, Susan C, Rochelle F, Marian M, Tracy D, Benjamin K, et al. Drug class review: disease-modifying drugs for multiple sclerosis: final update 1 report [Internet]. Portland (OR): Oregon Health & Science University, 2010. [: Available from: http://www.ncbi.nlm.nih.gov/books/NBK50570/]
Spiegelhalter 2002
Stangel 1999
Tiede 2003
  • Tiede I, Fritz G, Strand S, Poppe D, Dvorsky R, Strand D, et al. CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. The Journal of Clinical Investigation 2003;111:1133-45. [PUBMED: 12697733]
Vercellino 2009
  • Vercellino M, Masera S, Lorenzatti M, Condello C, Merola A, Mattioda A, et al. Demyelination, inflammation and neurodegeneration in multiple sclerosis deep gray matter. Journal of Neuropathology and Experimental Neurology 2009;68:489-502.
Weiner 1993
Yousry 2006
  • Yousry T, Major E, Ryschkewitsch C, Fahle G, Fischer S, Hou J, et al. Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy. The New England Journal of Medicine 2006;354(9):924-33. [PUBMED: 16510746]
Zintzaras 2012
  • Zintzaras E, Doxani C, Mprotsis T, Schmid CH, Hadjigeorgiou G. Network analysis of randomized controlled trials in multiple sclerosis. Clinical Therapeutics 2012;34(4):857-69.