Basic and escalating immunomodulatory treatments in multiple sclerosis: Current therapeutic recommendations

This review updates and extends earlier Consensus Reports related to current basic and escalating immunomodulatory treatments in multiple sclerosis (MS). The recent literature has been extracted for new evidence from randomized controlled trials, open treatment studies and reported expert opinion, both in original articles and reviews, and evaluates indications and safety issues based on published data. After data extraction from published full length publications and critically weighing the evidence and potential impact of the data, the review has been drafted and circulated within the National MS Societies and the European MS Platform to reach consensus within a very large group of European experts, combining evidence-based criteria and expert opinion where evidence is still incomplete. The review also outlines a few areas of controversy and delineates the need for future research.

[1]  D. Jeffery,et al.  A pilot trial of combination therapy with mitoxantrone and interferon beta-1b using monthly gadolinium-enhanced magnetic resonance imaging , 2005, Multiple sclerosis.

[2]  Thomas Berger,et al.  Lack of association between antimyelin antibodies and progression to multiple sclerosis. , 2007, The New England journal of medicine.

[3]  David H. Miller,et al.  A controlled trial of natalizumab for relapsing multiple sclerosis. , 2003, The New England journal of medicine.

[4]  S. Reingold,et al.  Multiple sclerosis diagnostic criteria: three years later , 2005, Multiple sclerosis.

[5]  T. Ziemssen Neuroprotection and glatiramer acetate: the possible role in the treatment of multiple sclerosis. , 2004, Advances in experimental medicine and biology.

[6]  S. Markovic-Plese,et al.  Longitudinal MRI study , 2003, Neurology.

[7]  F. Paul,et al.  Antibody to Aquaporin 4 in the Diagnosis of Neuromyelitis Optica , 2007, PLoS medicine.

[8]  L. Kappos,et al.  Interferon β-1a in relapsing multiple sclerosis: four-year extension of the European IFNβ-1a Dose-C omparison Study , 2004 .

[9]  H. Tremlett Randomized multicenter trial of natalizumab in acute MS relapses: Clinical and MRI effects , 2005, Neurology.

[10]  E. Cabanis,et al.  Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria. , 1997, Journal of neurology, neurosurgery, and psychiatry.

[11]  C. Pozzilli,et al.  Intravenous immunoglobulin in secondary progressive multiple sclerosis: randomised placebo-controlled trial , 2004, The Lancet.

[12]  Ichiro Nakashima,et al.  A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis , 2004, The Lancet.

[13]  A. Paolillo,et al.  Mitoxantrone treatment in patients with early relapsing-remitting multiple sclerosis , 2007, Multiple sclerosis.

[14]  J. Bouchard,et al.  Randomized study of once-weekly interferon β-1a therapy in relapsing multiple sclerosis: three-year data from the OWIMS study , 2005, Multiple sclerosis.

[15]  P. Sørensen Treatment of multiple sclerosis with intravenous immunoglobulin: review of clinical trials , 2003, Neurological Sciences.

[16]  A randomized study of two interferon-beta treatments in relapsing-remitting multiple sclerosis , 2006, Neurology.

[17]  Daniel J. Bauer,et al.  The reproductive effects of beta interferon therapy in pregnancy , 2005, Neurology.

[18]  D S Goodin,et al.  Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines , 2001 .

[19]  J. Rose,et al.  Treatment of multiple sclerosis with an anti–interleukin‐2 receptor monoclonal antibody , 2004, Annals of neurology.

[20]  V. Kuchroo,et al.  Discordant effects of anti-VLA-4 treatment before and after onset of relapsing experimental autoimmune encephalomyelitis. , 2001, The Journal of clinical investigation.

[21]  D. Figgitt,et al.  Mitoxantrone , 2004, CNS drugs.

[22]  D. Arnold,et al.  IM interferon β-1a delays definite multiple sclerosis 5 years after a first demyelinating event , 2006, Neurology.

[23]  K. Tyler,et al.  Through a glass, darkly: cerebrospinal fluid viral load measurements and the pathogenesis of human immunodeficiency virus infection of the central nervous system. , 2002, Archives of neurology.

[24]  V. Durkalski,et al.  Oral simvastatin treatment in relapsing-remitting multiple sclerosis , 2004, The Lancet.

[25]  D. Arnold,et al.  Rituximab in relapsing‐remitting multiple sclerosis: A 72‐week, open‐label, phase I trial , 2008, Annals of neurology.

[26]  P. Sørensen,et al.  Appearance and disappearance of neutralizing antibodies during interferon-beta therapy , 2005, Neurology.

[27]  J. Frederiksen,et al.  A randomized study of two interferon-beta treatments in relapsing-remitting multiple sclerosis. , 2006, Neurology.

[28]  J. Rose,et al.  Daclizumab phase II trial in relapsing and remitting multiple sclerosis , 2007, Neurology.

[29]  F. Sánchez‐Madrid,et al.  Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. , 1992, Nature.

[30]  D. Goodkin,et al.  A study of therapy-related acute leukaemia after mitoxantrone therapy for multiple sclerosis , 2002, Multiple sclerosis.

[31]  S. Nadeau,et al.  Diagnosis and management of dementia with Lewy bodies: Third report of the DLB Consortium , 2005, Neurology.

[32]  D. Goodin,et al.  Randomized, comparative study of interferon β-1a treatment regimens in MS , 2002, Neurology.

[33]  A. Achiron,et al.  Effect of intravenous immunoglobulin treatment on pregnancy and postpartum-related relapses in multiple sclerosis , 2004, Journal of Neurology.

[34]  H. Hartung,et al.  Expert opinion: Guidelines for the use of natalizumab in multiple sclerosis patients previously treated with immunomodulating therapies , 2007, Journal of Neuroimmunology.

[35]  T. Vartanian An examination of the results of the EVIDENCE, INCOMIN, and phase III studies of interferon beta products in the treatment of multiple sclerosis. , 2003, Clinical therapeutics.

[36]  A. Amato,et al.  Mycophenolate mofetil in dermatomyositis: Is it safe? , 2006, Neurology.

[37]  H. Hartung,et al.  [Revision of McDonald's new diagnostic criteria for multiple sclerosis]. , 2006, Der Nervenarzt.

[38]  I. Elovaara,et al.  The efficacy of glatiramer acetate in β‐interferon‐intolerant MS patients , 2005, Acta neurologica Scandinavica.

[39]  K. Albertsson-Wikland,et al.  Pubertal Growth Assessment , 2003, Hormone Research in Paediatrics.

[40]  Hans Lassmann,et al.  A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica. , 2002, Brain : a journal of neurology.

[41]  K. Hess,et al.  Escalating immunotherapy of multiple sclerosis--new aspects and practical application. , 2004, Journal of neurology.

[42]  D. Clifford,et al.  Rapid onset Mitoxantrone-induced cardiotoxicity in secondary progressive multiple sclerosis , 2003, Multiple sclerosis.

[43]  L. Kappos,et al.  Natalizumab treatment for multiple sclerosis: recommendations for patient selection and monitoring , 2007, The Lancet Neurology.

[44]  M. Rovaris,et al.  Randomized, double-blind, dose-comparison study of glatiramer acetate in relapsing–remitting MS , 2007, Neurology.

[45]  A. Gass,et al.  Escalating immunotherapy of multiple sclerosis , 2004, Journal of Neurology.

[46]  O. Khan,et al.  A prospective, open-label treatment trial to compare the effect of IFNβ-1a (Avonex®), IFNβ-1b (Betaseron®), and glatiramer acetate (Copaxone®) on the relapse rate in relapsing-remitting multiple sclerosis: results after 18 months of therapy , 2001, Multiple sclerosis.

[47]  C. Pozzilli,et al.  Guidelines on use of anti‐IFN‐β antibody measurements in multiple sclerosis: report of an EFNS Task Force on IFN‐β antibodies in multiple sclerosis , 2005, European journal of neurology.

[48]  Y. Itoyama,et al.  Clinical and MRI features of Japanese patients with multiple sclerosis positive for NMO-IgG , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[49]  H. Hartung,et al.  Plasma exchange in neuroimmunological disorders: Part 1: Rationale and treatment of inflammatory central nervous system disorders. , 2006, Archives of neurology.

[50]  Jiani Hu,et al.  Axonal metabolic recovery and potential neuroprotective effect of glatiramer acetate in relapsing-remitting multiple sclerosis , 2005, Multiple sclerosis.

[51]  D. Goodin Interferon beta in relapsing-remitting multiple sclerosis: an eight years experience in a specialist multiple sclerosis centre. , 2006, Journal of neurology.

[52]  E. Bonifacio,et al.  Similar low frequency of anti-MOG IgG and IgM in MS patients and healthy subjects , 2004, Neurology.

[53]  V. Tomassini,et al.  Predictors of long–term clinical response to interferon beta therapy in relapsing multiple sclerosis , 2006, Journal of Neurology.

[54]  D. Goodin,et al.  Benefits of high-dose, high-frequency interferon beta-1a in relapsing–remitting multiple sclerosis are sustained to 16 months: Final comparative results of the EVIDENCE trial , 2005, Journal of the Neurological Sciences.

[55]  David H. Miller,et al.  Application of the new McDonald criteria to patients with clinically isolated syndromes suggestive of multiple sclerosis , 2002, Annals of neurology.

[56]  F. Hanefeld,et al.  Treatment of early onset multiple sclerosis with subcutaneous interferon beta-1a , 2005, Neurology.

[57]  H. Waldmann,et al.  The window of therapeutic opportunity in multiple sclerosis , 2005, Journal of Neurology.

[58]  R. Ransohoff Natalizumab and PML , 2005, Nature Neuroscience.

[59]  A. Achiron,et al.  Intravenous immunoglobulin treatment following the first demyelinating event suggestive of multiple sclerosis: a randomized, double-blind, placebo-controlled trial. , 2004, Archives of neurology.

[60]  P. Sørensen,et al.  IV immunoglobulins as add-on treatment to methylprednisolone for acute relapses in MS , 2004, Neurology.

[61]  L. Pollak,et al.  Comparison of glatiramer acetate (Copaxone®) and interferon β-1b (Betaferon®) in multiple sclerosis patients: an open-label 2-year follow-up , 2002, Journal of the Neurological Sciences.

[62]  H. Hartung,et al.  Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial , 2002, The Lancet.

[63]  R. Gold,et al.  Plasma exchange for severe optic neuritis , 2004, Neurology.

[64]  R. Gold,et al.  Intravenous Immunoglobulins in MS. , 2005, International MS journal.

[65]  S. Reingold,et al.  Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria” , 2005, Annals of neurology.

[66]  Christian Confavreux,et al.  Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. , 2006, The New England journal of medicine.

[67]  G. Giovannoni,et al.  Anti-myelin antibodies do not allow earlier diagnosis of multiple sclerosis , 2005, Multiple sclerosis.

[68]  M. Sela,et al.  The immunomodulator glatiramer acetate augments the expression of neurotrophic factors in brains of experimental autoimmune encephalomyelitis mice. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[69]  F. Barkhof,et al.  Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy. , 2006, The New England journal of medicine.

[70]  J Sastre-Garriga,et al.  New diagnostic criteria for multiple sclerosis , 2003, Neurology.

[71]  F. Mihara,et al.  Heterogeneity of aquaporin-4 autoimmunity and spinal cord lesions in multiple sclerosis in Japanese. , 2007, Brain : a journal of neurology.

[72]  J. Zajicek,et al.  Campath 1-H treatment in patients with aggressive relapsing remitting multiple sclerosis , 2008, Journal of Neurology.

[73]  P. Adeleine,et al.  Risk of cancer from azathioprine therapy in multiple sclerosis , 1996, Neurology.

[74]  O. Khan,et al.  Effect of monthly intravenous cyclophosphamide in rapidly deteriorating multiple sclerosis patients resistant to conventional therapy , 2001, Multiple sclerosis.

[75]  A. Bertolotto Neutralizing antibodies to interferon beta: implications for the management of multiple sclerosis , 2004, Current opinion in neurology.

[76]  F Barkhof,et al.  Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes , 2006, Neurology.

[77]  P. Calabresi,et al.  An open-label trial of combination therapy with interferon β-1a and oral methotrexate in MS , 2002, Neurology.

[78]  P. Calabresi,et al.  Optimization of the safety and efficacy of interferon beta 1b and azathioprine combination therapy in multiple sclerosis , 2005, Multiple sclerosis.

[79]  S. Tenembaum,et al.  Interferon beta-1a treatment in childhood and juvenile-onset multiple sclerosis , 2006, Neurology.

[80]  C. Pozzilli,et al.  Disease-modifying drugs in childhood-juvenile multiple sclerosis: results of an Italian co-operative study , 2005, Multiple sclerosis.

[81]  L. Kappos,et al.  Interferon beta-1a in relapsing multiple sclerosis: four-year extension of the European IFNbeta-1a Dose-Comparison Study. , 2004, Multiple sclerosis.

[82]  P. Sørensen,et al.  Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis , 2003, The Lancet.

[83]  D. Arnold,et al.  B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. , 2008, The New England journal of medicine.

[84]  P. Vermersch,et al.  Mycophenolate mofetil and neurological diseases , 2005, Lupus.

[85]  L. Kappos,et al.  A randomized, double-blind, dose-comparison study of weekly interferon β-1a in relapsing MS , 2002, Neurology.

[86]  E. Frohman,et al.  Mycophenolate Mofetil in Multiple Sclerosis , 2004, Clinical neuropharmacology.

[87]  J S Wolinsky,et al.  EFNS guidelines on the use of neuroimaging in the management of multiple sclerosis , 2006, European journal of neurology.

[88]  M. Mascalchi,et al.  Early mitoxantrone-induced cardiotoxicity in secondary progressive multiple sclerosis , 2006 .

[89]  C. Poser,et al.  Diagnostic criteria for multiple sclerosis , 2001, Clinical Neurology and Neurosurgery.

[90]  O. Hommes,et al.  A dose comparison study of IVIG in postpartum relapsing-remitting multiple sclerosis , 2007, Multiple sclerosis.

[91]  T. Waldmann,et al.  Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon beta. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[92]  M. Freedman,et al.  Safety and tolerability of interferon beta-1b in pediatric multiple sclerosis , 2006, Neurology.

[93]  A. Compston,et al.  Recommended diagnostic criteria for multiple sclerosis: Guidelines from the international panel on the diagnosis of multiple sclerosis , 2001, Annals of neurology.

[94]  Ji‐Hyung Park,et al.  Prediction of early clinical severity and extent of neuronal damage in anterior-circulation infarction using the initial serum neuron-specific enolase level. , 2003, Archives of neurology.

[95]  Paul F. Smith Symptomatic treatment of multiple sclerosis using cannabinoids: recent advances , 2007, Expert review of neurotherapeutics.

[96]  M. Boggild,et al.  Sequential maintenance treatment with glatiramer acetate after mitoxantrone is safe and can limit exposure to immunosuppression in very active, relapsing remitting multiple sclerosis , 2006, Journal of Neurology.

[97]  L. Kappos,et al.  Neutralizing antibodies and efficacy of interferon β-1a , 2005, Neurology.

[98]  D. Jeffery Use of combination therapy with immunomodulators and immunosuppressants in treating multiple sclerosis , 2004, Neurology.

[99]  D. Simmons Anti-adhesion therapies. , 2005, Current opinion in pharmacology.

[100]  A. Ghezzi,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) , 2002, The Lancet.

[101]  L. Kappos,et al.  Visual and motor evoked potentials in the course of multiple sclerosis. , 2001, Brain : a journal of neurology.

[102]  L. Amaducci,et al.  Efficacy of azathioprine on multiple sclerosis new brain lesions evaluated using magnetic resonance imaging. , 2005, Archives of neurology.

[103]  H. Ulmer,et al.  Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. , 2003, The New England journal of medicine.

[104]  E. Leray,et al.  Mitoxantrone as induction treatment in aggressive relapsing remitting multiple sclerosis: treatment response factors in a 5 year follow-up observational study of 100 consecutive patients , 2007, Journal of Neurology, Neurosurgery, and Psychiatry.

[105]  Selective treatment of multiple sclerosis. , 2006, The New England journal of medicine.

[106]  Ludwig Kappos,et al.  A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. , 2006, The New England journal of medicine.

[107]  G. Rice,et al.  Interferon β-1a in MS , 2005, Neurology.

[108]  C. Pozzilli,et al.  Neutralizing antibodies during treatment of secondary progressive MS with interferon β-1b , 2003, Neurology.

[109]  K. Khalili,et al.  Human demyelinating disease and the polyomavirus JCV , 2006, Multiple sclerosis.

[110]  Massimo Filippi,et al.  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 , 2006, The Lancet Neurology.

[111]  Antibodies against glycosylated native MOG are elevated in patients with multiple sclerosis. , 2004, Neurology.

[112]  H. Hartung,et al.  Immune response to immunotherapy: the role of neutralising antibodies to interferon beta in the treatment of multiple sclerosis , 2005, The Lancet Neurology.

[113]  J. Haas High Dose IVIG in the Post Partum Period for Prevention of Exacerbations in MS , 2000, Multiple sclerosis.

[114]  Geneva,et al.  Pregnancy outcomes during treatment with interferon beta-1a in patients with multiple sclerosis , 2005, Neurology.

[115]  R. Scheyer,et al.  A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses , 2006, Neurology.

[116]  Ludwig Kappos,et al.  Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study , 2007, The Lancet.

[117]  Xingchang Wei,et al.  A randomized blinded trial of combination therapy with cyclophosphamide in patients with active multiple sclerosis on interferon beta , 2005, Multiple sclerosis.

[118]  D. Goodin,et al.  Enhanced benefit of increasing interferon beta-1a dose and frequency in relapsing multiple sclerosis: the EVIDENCE Study. , 2005, Archives of neurology.

[119]  D. Goodkin,et al.  Cardiac adverse effects associated with mitoxantrone (Novantrone) therapy in patients with MS , 2002, Neurology.

[120]  H P Hartung,et al.  Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes , 2006, Neurology.

[121]  G. Comi,et al.  MS treatment: New perspectives , 2006, Clinical Neurology and Neurosurgery.

[122]  M. Reindl,et al.  Antimyelin antibodies and the risk of relapse in patients with a primary demyelinating event , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[123]  D. Goodin A randomized study of two interferon-beta treatments in relapsing-remitting multiple sclerosis , 2006, Neurology.

[124]  J. Sipe Cladribine for multiple sclerosis: review and current status , 2005, Expert review of neurotherapeutics.

[125]  J. Stockman,et al.  Oral Fingolimod (FTY720) for Relapsing Multiple Sclerosis , 2008 .

[126]  J. Haas,et al.  Twenty‐four‐month comparison of immunomodulatory treatments – a retrospective open label study in 308 RRMS patients treated with beta interferons or glatiramer acetate (Copaxone®) , 2005, European journal of neurology.

[127]  P. Narayana,et al.  Glatiramer acetate in primary progressive multiple sclerosis: Results of a multinational, multicenter, double‐blind, placebo‐controlled trial , 2007, Annals of neurology.

[128]  P. Rieckmann,et al.  Early abnormalities of evoked potentials and future disability in patients with multiple sclerosis , 2006, Multiple sclerosis.

[129]  M. Calabrese,et al.  Mitoxantrone versus cyclophosphamide in secondary-progressive multiple sclerosis , 2006, Journal of Neurology.

[130]  M. Atkins,et al.  Melanoma complicating treatment with natalizumab for multiple sclerosis. , 2008, The New England journal of medicine.