Impact of diagnosis and early treatment on the course of multiple sclerosis.

Multiple sclerosis (MS) is a progressive inflammatory disease of the central nervous system that results in neurological dysfunction and disability. The initiation of disease-modifying therapy (DMT) early in the course of MS may improve the prognosis for patients with MS and reduce the occurrence of neurological damage. In patients with relapsing-remitting MS (RRMS), DMT reduces the rate of relapses, reduces the appearance of magnetic resonance imaging markers of disease activity, and slows the course of disability progression. DMT has been shown to be more effective when initiated early in the course of MS. In patients who have not yet developed clinically definite MS (CDMS), but have had 1 attack of neurological symptoms consistent with MS (ie, clinically isolated syndrome [CIS]), the initiation of DMT (specifically, interferon beta, glatiramer acetate, and teriflunomide) following this attack has been shown to delay the conversion to CDMS. Current guidelines have recognized the benefits of early treatment of MS with DMTs. However, there are a number of barriers to implementing early MS treatment. Early diagnosis and treatment of MS can be hindered because patients may delay consulting a physician about their neurological symptoms or may be reluctant to start DMT. Further, even after initiating DMT, continued adherence to treatment is often poor. These delays in treatment and a lack of adherence to treatment are associated with poor patient outcomes. The objectives of this review are to highlight the importance of early diagnosis and treatment of CIS or RRMS and discuss the favorable outcomes associated with early initiation of DMT.

[1]  K. Moreo,et al.  Managed approaches to multiple sclerosis in special populations. , 2015, Journal of managed care pharmacy : JMCP.

[2]  Jeremy A Schafer,et al.  Association of Prescription Abandonment with Cost Share for High-Cost Specialty Pharmacy Medications , 2009, Journal of managed care pharmacy : JMCP.

[3]  Hirofumi Ochi,et al.  [Cognitive impairment in multiple sclerosis]. , 2014, Brain and nerve = Shinkei kenkyu no shinpo.

[4]  L. Kappos,et al.  Magnetic resonance imaging outcomes from a phase III trial of teriflunomide , 2013, Multiple sclerosis.

[5]  D. Arnold,et al.  Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. , 2012, The New England journal of medicine.

[6]  David H. Miller,et al.  Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. , 2012, The New England journal of medicine.

[7]  P. Gustafson,et al.  Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis. , 2012, JAMA.

[8]  Bernhard Hemmer,et al.  Potassium channel KIR4.1 as an immune target in multiple sclerosis. , 2012, The New England journal of medicine.

[9]  L. Kappos,et al.  Teriflunomide added to interferon-β in relapsing multiple sclerosis , 2012, Neurology.

[10]  L. Kappos,et al.  Additional efficacy endpoints from pivotal natalizumab trials in relapsing-remitting MS , 2012, Journal of Neurology.

[11]  F. Barkhof,et al.  Early Initiation of Interferon Beta-1b after a First Clinical Event Suggestive of Multiple Sclerosis: Clinical Outcomes and Use of Disease-Modifying Therapy from the BENEFIT Extension Study (PD5.002) , 2012 .

[12]  R. Kinkel,et al.  Association between immediate initiation of intramuscular interferon beta-1a at the time of a clinically isolated syndrome and long-term outcomes: a 10-year follow-up of the Controlled High-Risk Avonex Multiple Sclerosis Prevention Study in Ongoing Neurological Surveillance. , 2012, Archives of neurology.

[13]  X. Montalban,et al.  Risk stratification for progressive multifocal leukoencephalopathy in patients treated with natalizumab , 2012, Multiple sclerosis.

[14]  Ludwig Kappos,et al.  Comparison of two dosing frequencies of subcutaneous interferon beta-1a in patients with a first clinical demyelinating event suggestive of multiple sclerosis (REFLEX): a phase 3 randomised controlled trial , 2012, The Lancet Neurology.

[15]  M. Mäurer,et al.  Natalizumab May Improve Cognition and Mood in Multiple Sclerosis , 2012, European Neurology.

[16]  David Hunt,et al.  Natalizumab-associated progressive multifocal leucoencephalopathy: a practical approach to risk profiling and monitoring , 2012, Practical Neurology.

[17]  Anthony Traboulsee,et al.  Relationship between early clinical characteristics and long term disability outcomes: 16 year cohort study (follow-up) of the pivotal interferon β-1b trial in multiple sclerosis , 2011, Journal of Neurology, Neurosurgery & Psychiatry.

[18]  C. Polman,et al.  Oral treatment for multiple sclerosis , 2011, The Lancet Neurology.

[19]  X. Montalban,et al.  IL28B polymorphisms are not associated with the response to interferon-beta in multiple sclerosis , 2011, Journal of Neuroimmunology.

[20]  Christian Confavreux,et al.  Randomized trial of oral teriflunomide for relapsing multiple sclerosis. , 2011, The New England journal of medicine.

[21]  Jeffrey A. Cohen,et al.  Potential mechanisms of efficacy and adverse effects in the use of fingolimod (FTY720) , 2011, Expert review of clinical pharmacology.

[22]  N. Putzki,et al.  The interferon beta therapies for treatment of relapsing–remitting multiple sclerosis: are they equally efficacious? A comparative review of open-label studies evaluating the efficacy, safety, or dosing of different interferon beta formulations alone or in combination , 2011, Therapeutic advances in neurological disorders.

[23]  Ramil N. Nurtdinov,et al.  Search for Specific Biomarkers of IFNβ Bioactivity in Patients with Multiple Sclerosis , 2011, PloS one.

[24]  A. Chappel,et al.  Cost-effectiveness of disease-modifying therapy for multiple sclerosis , 2011, Neurology.

[25]  H. Weiner,et al.  Cognitive deterioration in patients with early multiple sclerosis: a 5-year study , 2011, Journal of Neurology, Neurosurgery & Psychiatry.

[26]  Jared M. Bruce,et al.  Multiple sclerosis: MS treatment adherence—how to keep patients on medication? , 2011, Nature Reviews Neurology.

[27]  J. Berger Functional improvement and symptom management in multiple sclerosis: clinical efficacy of current therapies. , 2011, The American journal of managed care.

[28]  T. Gomes,et al.  Adherence to Multiple Sclerosis Disease-Modifying Therapies in Ontario is Low , 2011, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[29]  M. Kita FDA-approved preventative therapies for MS: first-line agents. , 2011, Neurologic clinics.

[30]  N. Sicotte Magnetic resonance imaging in multiple sclerosis: the role of conventional imaging. , 2011, Neurologic clinics.

[31]  H. Hartung,et al.  Influence of the HLA-DRB1 genotype on antibody development to interferon beta in multiple sclerosis. , 2011, Archives of neurology.

[32]  M. Hutchinson,et al.  Multiple sclerosis, from referral to confirmed diagnosis: an audit of clinical practice , 2011, Multiple sclerosis.

[33]  S. Krieger Multiple sclerosis therapeutic pipeline: opportunities and challenges. , 2011, The Mount Sinai journal of medicine, New York.

[34]  J. Derwenskus Current disease-modifying treatment of multiple sclerosis. , 2011, The Mount Sinai journal of medicine, New York.

[35]  Nathalie Girouard,et al.  Patient considerations in the management of multiple sclerosis: development and clinical utility of oral agents , 2011, Patient preference and adherence.

[36]  Jeffrey A. Cohen,et al.  Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria , 2011, Annals of neurology.

[37]  C. Enzinger,et al.  Cognitive impairment in relation to MRI metrics in patients with clinically isolated syndrome , 2011, Multiple sclerosis.

[38]  Amy Perrin Ross,et al.  Recent Developments in the Early Diagnosis and Management of Multiple Sclerosis , 2010, The Journal of neuroscience nursing : journal of the American Association of Neuroscience Nurses.

[39]  O. Gout,et al.  Prior suggestive symptoms in one-third of patients consulting for a “first” demyelinating event , 2010, Journal of Neurology, Neurosurgery & Psychiatry.

[40]  Jeremy A Schafer,et al.  Price Increases and New Drugs Drive Increased Expenditures for Multiple Sclerosis , 2010, Journal of managed care pharmacy : JMCP.

[41]  G. Comi,et al.  Evolving expectations around early management of multiple sclerosis , 2010, Therapeutic advances in neurological disorders.

[42]  J. Ranjeva,et al.  Frequency of cognitive impairment dramatically increases during the first 5 years of multiple sclerosis , 2010, Journal of Neurology, Neurosurgery & Psychiatry.

[43]  F. Barkhof,et al.  Early central atrophy rate predicts 5 year clinical outcome in multiple sclerosis , 2010, Journal of Neurology, Neurosurgery & Psychiatry.

[44]  K. Simon,et al.  Anti‐JC virus antibodies: Implications for PML Risk Stratification , 2010, Annals of neurology.

[45]  George C. Ebers,et al.  The natural history of multiple sclerosis, a geographically based study 10: relapses and long-term disability , 2010, Brain : a journal of neurology.

[46]  T. Scott,et al.  Poor recovery after the first two attacks of multiple sclerosis is associated with poor outcome five years later , 2010, Journal of the Neurological Sciences.

[47]  Helen Tremlett,et al.  Factors associated with delay to medical recognition in two Canadian multiple sclerosis cohorts , 2010, Journal of the Neurological Sciences.

[48]  G. Izquierdo,et al.  Characteristics of multiple sclerosis at onset and delay of diagnosis and treatment in Spain (The Novo Study) , 2010, Journal of Neurology.

[49]  Ludwig Kappos,et al.  A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. , 2010, The New England journal of medicine.

[50]  Ludwig Kappos,et al.  Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. , 2010, The New England journal of medicine.

[51]  R. Marrie,et al.  Impact of loss of mobility on instrumental activities of daily living and socioeconomic status in patients with MS , 2010, Current medical research and opinion.

[52]  David H. Miller,et al.  Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial , 2009, The Lancet Neurology.

[53]  F Fazekas,et al.  Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial , 2009, The Lancet.

[54]  M. Filippi,et al.  250 μg or 500 μg interferon beta-1b versus 20 mg glatiramer acetate in relapsing-remitting multiple sclerosis: a prospective, randomised, multicentre study , 2009, The Lancet Neurology.

[55]  D. Goodin,et al.  Review: Treatment of early multiple sclerosis: the value of treatment initiation after a first clinical episode , 2009, Multiple sclerosis.

[56]  J. Skurnick,et al.  Efficacy of treatment of MS with IFN -1b or glatiramer acetate by monthly brain MRI in the BECOME study , 2009 .

[57]  M. Kremenchutzky,et al.  Efficacy of intramuscular interferon beta-1a in patients with clinically isolated syndrome: analysis of subgroups based on new risk criteria , 2009, Multiple sclerosis.

[58]  J. Fischer,et al.  Quality of life in 1000 patients with early relapsing–remitting multiple sclerosis , 2009, European journal of neurology.

[59]  R. Marrie,et al.  Comorbidity delays diagnosis and increases disability at diagnosis in MS , 2009, Neurology.

[60]  U. Webb Early Interferon Beta Treatment in Multiple Sclerosis: Nursing Care Implications of the BENEFIT Study , 2008, The Journal of neuroscience nursing : journal of the American Association of Neuroscience Nurses.

[61]  Ludwig Kappos,et al.  Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study , 2008, The Lancet.

[62]  F. Barkhof,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 , 2008, The Lancet Neurology.

[63]  C. Constantinescu,et al.  Spotlight on teriflunomide. , 2008, International MS journal.

[64]  M. Tintoré,et al.  Recombinant interferon beta or glatiramer acetate for delaying conversion of the first demyelinating event to multiple sclerosis. , 2008, The Cochrane database of systematic reviews.

[65]  C. Polman,et al.  Pharmacogenomics of Interferon-ß Therapy in Multiple Sclerosis: Baseline IFN Signature Determines Pharmacological Differences between Patients , 2008, PloS one.

[66]  F. Barkhof,et al.  Subgroups of the BENEFIT study: Risk of developing MS and treatment effect of interferon beta-1b , 2008, Journal of Neurology.

[67]  G. Comi Clinically isolated syndrome: the rationale for early treatment , 2008, Nature Clinical Practice Neurology.

[68]  M. Ron,et al.  Cognitive impairment in multiple sclerosis can be predicted by imaging early in the disease , 2008, Journal of Neurology, Neurosurgery, and Psychiatry.

[69]  Pablo Villoslada,et al.  Genome-wide pharmacogenomic analysis of the response to interferon beta therapy in multiple sclerosis. , 2008, Archives of neurology.

[70]  B. Brochet,et al.  Unexpected multiple sclerosis: follow-up of 30 patients with magnetic resonance imaging and clinical conversion profile , 2008, Journal of Neurology, Neurosurgery, and Psychiatry.

[71]  L. Durelli,et al.  MRI activity and neutralising antibody as predictors of response to interferon β treatment in multiple sclerosis , 2007, Journal of Neurology, Neurosurgery, and Psychiatry.

[72]  M. Filippi,et al.  Inflammatory demyelination and neurodegeneration in early multiple sclerosis , 2007, Journal of the Neurological Sciences.

[73]  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.

[74]  M. Sahraian,et al.  Effect of early interferon beta‐1a therapy on conversion to multiple sclerosis in Iranian patients with a first demyelinating event , 2007, Acta neurologica Scandinavica.

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

[76]  S. Fereshtehnejad,et al.  The effect of interferon-beta1a on relapses and progression of disability in patients with clinically isolated syndromes (CIS) suggestive of multiple sclerosis , 2007, Clinical Neurology and Neurosurgery.

[77]  L. Kappos,et al.  MRI outcomes in a placebo-controlled trial of natalizumab in relapsing MS , 2007, Neurology.

[78]  L. Kappos,et al.  Natalizumab reduces visual loss in patients with relapsing multiple sclerosis , 2007, Neurology.

[79]  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.

[80]  D. Goodin IM interferon β-1a delays definite multiple sclerosis 5 years after a first demyelinating event , 2006, Neurology.

[81]  À. Rovira,et al.  Baseline MRI predicts future attacks and disability in clinically isolated syndromes , 2006, Neurology.

[82]  Ludwig Kappos,et al.  Oral fingolimod (FTY720) for relapsing multiple sclerosis. , 2006, The New England journal of medicine.

[83]  V. Shaygannejad,et al.  Comparison of Betaferon, Avonex, and Rebif in treatment of relapsing–remitting multiple sclerosis , 2006, Acta neurologica Scandinavica.

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

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

[86]  X. Montalban,et al.  Defining the response to interferon‐β in relapsing‐remitting multiple sclerosis patients , 2006, Annals of neurology.

[87]  Michael Hutchinson,et al.  Pharmacogenomics of responsiveness to interferon IFN‐β treatment in multiple sclerosis: A genetic screen of 100 type I interferon‐inducible genes , 2005, Clinical pharmacology and therapeutics.

[88]  P. Rieckmann Neurodegeneration and clinical relevance for early treatment in multiple sclerosis. , 2005, International MS journal.

[89]  A. Thompson,et al.  Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis , 2005, The Lancet Neurology.

[90]  Peter A Calabresi,et al.  Diagnosis and management of multiple sclerosis. , 2004, American family physician.

[91]  Marco Rovaris,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 , 2004, The Lancet.

[92]  L. Weiner,et al.  Glatiramer acetate (Copaxone): comparison of continuous versus delayed therapy in a six-year organized multiple sclerosis trial , 2003, Multiple sclerosis.

[93]  P. O'Connor The effects of intramuscular interferon beta-Ia in patients at high risk for development of multiple sclerosis: a post hoc analysis of data from CHAMPS. , 2003, Clinical therapeutics.

[94]  C. Pozzilli,et al.  Home based management in multiple sclerosis: results of a randomised controlled trial , 2002, Journal of neurology, neurosurgery, and psychiatry.

[95]  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.

[96]  D. Goodin,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 , 2002 .

[97]  Marco Rovaris,et al.  Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study , 2001, The Lancet.

[98]  Massimo Filippi,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 , 2001, Annals of neurology.

[99]  J H Simon,et al.  Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. , 2000, The New England journal of medicine.

[100]  C. Granger,et al.  Intramuscular interferon beta‐1a for disease progression in relapsing multiple sclerosis , 1996, Annals of neurology.

[101]  B. Hemmer,et al.  Current treatment strategies for multiple sclerosis - efficacy versus neurological adverse effects. , 2012, Current pharmaceutical design.

[102]  K. Meyer,et al.  Approaches to the Management of Agents Used for the Treatment of Multiple Sclerosis: Consensus Statements from a Panel of U.S. Managed Care Pharmacists and Physicians , 2012, Journal of managed care pharmacy : JMCP.

[103]  M. McDonagh,et al.  Drug Class Review: Disease-modifying Drugs for Multiple Sclerosis: Final Update 1 Report , 2010 .

[104]  M. Wallin Integrated multiple sclerosis care: new approaches and paradigm shifts. , 2010, Journal of rehabilitation research and development.

[105]  J. Castelli-Haley,et al.  Cost sharing, benefit design, and adherence: the case of multiple sclerosis. , 2010, Advances in health economics and health services research.

[106]  P. Fontoura,et al.  Multiple sclerosis therapies: molecular mechanisms and future. , 2010, Results and problems in cell differentiation.

[107]  J. Halper Consortium of Multiple Sclerosis Centers , 2005 .

[108]  S. Galetta,et al.  US FDA-Approved Disease-Modifying Treatments for Multiple Sclerosis , 2005, CNS drugs.

[109]  E. Byrne Randomized, comparative study of interferon beta-1a treatment regimens in MS: the EVIDENCE trial. , 2002, Neurology.

[110]  Jeffrey A. Cohen,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. , 1995, Neurology.

[111]  W. L. Benedict,et al.  Multiple Sclerosis , 2007, Journal - Michigan State Medical Society.