title: Disease modifying therapies for relapsing multiple sclerosis.
abstract: Multiple sclerosis (MS) is a common, disabling, putatively autoimmune neurological disease with worldwide distribution. It typically begins as a relapsing disorder that later evolves to a secondary progressive phase. Inflammatory and neurodegenerative mechanisms seem to operate in both phases, but their relative contributions and interactions are incompletely understood. Disease modifying therapies (DMTs) approved for relapsing multiple sclerosis interfere with a variety of immunological mechanisms to reduce rates of relapse, accumulation of disease burden measured by magnetic resonance imaging (MRI), and decline in neurological function over the two to three year duration of typical randomized controlled trials. Benefits of longer duration of therapy on disability are less clear, as data beyond three years are largely limited to observational studies. However, current DMTs do not slow accrual of disability once progressive multiple sclerosis is established. This review summarizes the evidence about the use of approved DMTs and examines how to individualize treatment despite the absence of validated biomarkers to guide drug selection. Methods such as stratifying patients on the basis of estimated risk for future disability, weighing patient specific factors and preferences, and using objective outcomes to adjudicate treatment success are discussed. Emerging drug therapies and strategies are also reviewed.
authors.affiliation: Department of Neurology, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ, 85259, USA wingerchuk.dean@mayo.edu.
authors.forename: Dean M
authors.initials: DM
authors.lastname: Wingerchuk
authors.affiliation: Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Weinshenker
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D003437:Crotonates / Q000627:therapeutic use; D000077561:Daclizumab; D000069462:Dimethyl Fumarate / Q000627:therapeutic use; D057915:Drug Substitution; D000068876:Fingolimod Hydrochloride / Q000627:therapeutic use; D000068717:Glatiramer Acetate / Q000627:therapeutic use; D006801:Humans; D006885:Hydroxybutyrates; D007074:Immunoglobulin G / Q000627:therapeutic use; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D007267:Injections; D016899:Interferon-beta / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008942:Mitoxantrone / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D000069442:Natalizumab / Q000627:therapeutic use; D009570:Nitriles; D014052:Toluidines / Q000627:therapeutic use
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003437:Crotonates; D006885:Hydroxybutyrates; D007074:Immunoglobulin G; D007155:Immunologic Factors; D000069442:Natalizumab; D009570:Nitriles; D014052:Toluidines; C527525:teriflunomide; D000074323:Alemtuzumab; D000068717:Glatiramer Acetate; D016899:Interferon-beta; D008942:Mitoxantrone; D000077561:Daclizumab; D000069462:Dimethyl Fumarate; D000068876:Fingolimod Hydrochloride