Therapeutic Decision Making in a New Drug Era in Multiple Sclerosis

 

 Permissions and Reprints

Abstract

Multiple sclerosis is a presumed autoimmune, inflammatory disease of the central nervous system. Since the early 1990s, medications have been devised, tested, and approved for relapsing forms of multiple sclerosis (MS). MS treatments work by altering the immune system to reduce inflammatory MS activity, thus curtailing clinical relapses (attacks), thereby reducing short-term disability related to the MS attacks. The promise of long-term improvement in MS-related disability remains the most desirable therapeutic goal; to what degree current MS therapies are effective in reducing this is controversial. Recent years have seen a surge in novel MS therapies delivered both parenterally and orally that offer new therapeutic alternatives to MS patients and their treating providers. It remains essential to make an unequivocal diagnosis of MS and identify its clinical course prior to initiating therapies. Switching and altering MS therapies can now be done by rational approaches based on therapeutic efficacy and tolerability; however, these remain nonevidence-based for the most part. The high cost of MS therapies remains a significant concern. A new therapeutic era is at hand offering new hope for patients affected by this chronic, frequently disabling disease.

• References

• 1 Polman CH, Reingold SC, Banwell B , et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69 (2) 292-302
  CrossrefPubMedGoogle Scholar
• 2 Beck RW, Cleary PA, Anderson Jr MM , et al; The Optic Neuritis Study Group. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. N Engl J Med 1992; 326 (9) 581-588
  CrossrefPubMedGoogle Scholar
• 3 Metz LM, Sabuda D, Hilsden RJ, Enns R, Meddings JB. Gastric tolerance of high-dose pulse oral prednisone in multiple sclerosis. Neurology 1999; 53 (9) 2093-2096
  CrossrefPubMedGoogle Scholar
• 4 Staff NP, Lucchinetti CF, Keegan BM. Multiple sclerosis with predominant, severe cognitive impairment. Arch Neurol 2009; 66 (9) 1139-1143
  CrossrefPubMedGoogle Scholar
• 5 Barkhof F, Rocca M, Francis G , et al; Early Treatment of Multiple Sclerosis Study Group. Validation of diagnostic magnetic resonance imaging criteria for multiple sclerosis and response to interferon beta1a. Ann Neurol 2003; 53 (6) 718-724
  CrossrefPubMedGoogle Scholar
• 6 Fortini AS, Sanders EL, Weinshenker BG, Katzmann JA. Cerebrospinal fluid oligoclonal bands in the diagnosis of multiple sclerosis. Isoelectric focusing with IgG immunoblotting compared with high-resolution agarose gel electrophoresis and cerebrospinal fluid IgG index. Am J Clin Pathol 2003; 120 (5) 672-675
  CrossrefPubMedGoogle Scholar
• 7 Gronseth GS, Ashman EJ. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: the usefulness of evoked potentials in identifying clinically silent lesions in patients with suspected multiple sclerosis (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000; 54 (9) 1720-1725
  CrossrefPubMedGoogle Scholar
• 8 Miller DH, Weinshenker BG, Filippi M , et al. Differential diagnosis of suspected multiple sclerosis: a consensus approach. Mult Scler 2008; 14 (9) 1157-1174
  CrossrefPubMedGoogle Scholar
• 9 Okuda DT, Mowry EM, Beheshtian A , et al. Incidental MRI anomalies suggestive of multiple sclerosis: the radiologically isolated syndrome. [see comment][erratum appears in Neurology. 2009 Apr 7;72(14):1284] Neurology 2009; 72 (9) 800-805
  CrossrefPubMedGoogle Scholar
• 10 Siva A, Saip S, Altintas A, Jacob A, Keegan BM, Kantarci OH. Multiple sclerosis risk in radiologically uncovered asymptomatic possible inflammatory-demyelinating disease. Mult Scler 2009; 15 (8) 918-927
  CrossrefPubMedGoogle Scholar
• 11 Okuda DT, Mowry EM, Cree BAC , et al. Asymptomatic spinal cord lesions predict disease progression in radiologically isolated syndrome. Neurology 2011; 76 (8) 686-692
  CrossrefPubMedGoogle Scholar
• 12 Miller D, Barkhof F, Montalban X, Thompson A, Filippi M. Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis. Lancet Neurol 2005; 4 (5) 281-288
  CrossrefPubMedGoogle Scholar
• 13 Miller D, Barkhof F, Montalban X, Thompson A, Filippi M. Clinically isolated syndromes suggestive of multiple sclerosis, part 2: non-conventional MRI, recovery processes, and management. Lancet Neurol 2005; 4 (6) 341-348
  CrossrefPubMedGoogle Scholar
• 14 Jacobs LD, Beck RW, Simon JH , et al; CHAMPS Study Group. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. N Engl J Med 2000; 343 (13) 898-904
  CrossrefPubMedGoogle Scholar
• 15 Kappos L, Freedman MS, Polman CH , et al; BENEFIT Study Group. 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. Lancet 2007; 370 (9585) 389-397
  CrossrefPubMedGoogle Scholar
• 16 Comi G, Martinelli V, Rodegher M , et al; PreCISe study group. 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. Lancet 2009; 374 (9700) 1503-1511
  CrossrefPubMedGoogle Scholar
• 17 Miller DH, Leary SM. Primary-progressive multiple sclerosis. Lancet Neurol 2007; 6 (10) 903-912
  CrossrefPubMedGoogle Scholar
• 18 Wolinsky JS, Narayana PA, O'Connor P , et al; PROMiSe Trial Study Group. Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol 2007; 61 (1) 14-24
  CrossrefPubMedGoogle Scholar
• 19 Goodin DS, Reder AT, Ebers GC , et al. Survival in MS: a randomized cohort study 21 years after the start of the pivotal IFNβ-1b trial. Neurology 2012; 78 (17) 1315-1322
  CrossrefPubMedGoogle Scholar
• 20 Shirani A, Zhao Y, Karim ME , et al. Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis. JAMA 2012; 308 (3) 247-256
  CrossrefPubMedGoogle Scholar
• 21 Mikol DD, Barkhof F, Chang P , et al; REGARD study group. 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 Neurol 2008; 7 (10) 903-914
  CrossrefPubMedGoogle Scholar
• 22 Lublin FD, Cofield SS, Cutter GR , et al; for the CombiRx Investigators. Randomized study combining interferon and glatiramer acetate in multiple sclerosis. Ann Neurol 2013;
  PubMedGoogle Scholar
• 23 Cohen JA, Barkhof F, Comi G , et al; TRANSFORMS Study Group. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 2010; 362 (5) 402-415
  CrossrefPubMedGoogle Scholar
• 24 O'Connor P, Wolinsky JS, Confavreux C , et al; TEMSO Trial Group. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med 2011; 365 (14) 1293-1303
  CrossrefPubMedGoogle Scholar
• 25 Pelletier D, Hafler DA. Fingolimod for multiple sclerosis. N Engl J Med 2012; 366 (4) 339-347
  CrossrefPubMedGoogle Scholar
• 26 Goodin DS, Cohen BA, O'Connor P, Kappos L, Stevens JC. Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Assessment: the use of natalizumab (Tysabri) for the treatment of multiple sclerosis (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2008; 71 (10) 766-773
  CrossrefPubMedGoogle Scholar
• 27 Kleinschmidt-DeMasters BK, Miravalle A, Schowinsky J, Corboy J, Vollmer T. Update on PML and PML-IRIS occurring in multiple sclerosis patients treated with natalizumab. J Neuropathol Exp Neurol 2012; 71 (7) 604-617
  CrossrefPubMedGoogle Scholar
• 28 Khatri BO, Man S, Giovannoni G , et al. Effect of plasma exchange in accelerating natalizumab clearance and restoring leukocyte function. Neurology 2009; 72 (5) 402-409
  CrossrefPubMedGoogle Scholar
• 29 Tan IL, McArthur JC, Clifford DB, Major EO, Nath A. Immune reconstitution inflammatory syndrome in natalizumab-associated PML. Neurology 2011; 77 (11) 1061-1067
  CrossrefPubMedGoogle Scholar
• 30 Coles AJ, Compston DA, Selmaj KW , et al; CAMMS223 Trial Investigators. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med 2008; 359 (17) 1786-1801
  Google Scholar
• 31 Coles AJ, Twyman CL, Arnold DL , et al; CARE-MS II investigators. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet 2012; 380 (9856) 1829-1839
  CrossrefPubMedGoogle Scholar
• 32 Boster A, Edan G, Frohman E , et al; Multiple Sclerosis Clinical Research Center, Department of Neurology, Wayne State University School of Medicine. Intense immunosuppression in patients with rapidly worsening multiple sclerosis: treatment guidelines for the clinician. Lancet Neurol 2008; 7 (2) 173-183
  CrossrefPubMedGoogle Scholar
• 33 Hauser SL, Waubant E, Arnold DL , et al; HERMES Trial Group. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 2008; 358 (7) 676-688
  CrossrefPubMedGoogle Scholar
• 34 Panitch H, Goodin DS, Francis G , et al; EVIDENCE Study Group. 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 (10) 1496-1506
  CrossrefPubMedGoogle Scholar
• 35 van der Voort LF, Gilli F, Bertolotto A , et al. Clinical effect of neutralizing antibodies to interferon beta that persist long after cessation of therapy for multiple sclerosis. Arch Neurol 2010; 67 (4) 402-407
  CrossrefPubMedGoogle Scholar
• 36 Pittock SJ, Weinshenker BG, Noseworthy JH , et al. Not every patient with multiple sclerosis should be treated at time of diagnosis. [see comment] Arch Neurol 2006; 63 (4) 611-614
  CrossrefPubMedGoogle Scholar