title: Disease-modifying Therapies for Multiple Sclerosis.
abstract: Multiple sclerosis (MS) is likely an autoimmune disorder, although this remains unproven. Immunotherapeutic treatments have been shown to be helpful, especially in relapsing forms of the illness, but the treatments are incomplete, and many patients continue to worsen over time, even with standard therapy. Immunotherapies presently available appear to have their greatest effect when used early in the course of the illness. In relapsing-remitting multiple sclerosis (RRMS), there is overwhelming Class I data from large clinical trials that supports the use of interferon-beta-1a (IFNbeta-1a), interferon-beta-1b (IFNbeta-1b), and glatiramer acetate. Comparative data are limited, and results published in different trials support the idea that treatment outcomes with the various drugs are more similar than different. Decisions about treatment choice should be tailored to the needs of the individual patient. With the exception of a small number of patients with benign MS, all RRMS patients should be treated with one of the interferons or glatiramer acetate. There are Class I data consistent with the idea that higher dose or more frequent administration of interferon-beta (IFNbeta) is associated with better clinical outcome and reduced progression of changes on brain MRI scans. The duration of this effect is not clear, and higher dose with more frequent administration is associated with higher cost, more side effects, and greater production of interferon antibodies. Interferon antibodies possibly reduce efficacy of IFNbeta in RRMS and secondary progressive multiple sclerosis (SPMS). Clinically isolated syndromes (CIS) of demyelination in the central nervous system can be reliably diagnosed, and the risk of further episodes of demyelination is consistent with the diagnosis of RRMS stratified by use of brain MRI scans. Patients at high risk of developing RRMS after CIS achieve significant benefit after treatment with IFNbeta-1a, and initiation of therapy after CIS should be given strong consideration. There are no similar data for IFNbeta-1b or glatiramer acetate, but logic would dictate a similar response with these agents. In SPMS, there are Class I data that treatment with IFNbeta-1a or IFNbeta-1b has a significant effect on progression of brain MRI lesions, but clinical outcomes are less clearly affected. It is justifiable to treat SPMS patients with IFNbeta. Mitoxantrone may be effective in slowing progression of SPMS, and its risks are moderate. It should be used in patients with SPMS, but potential long-term risks must be discussed with the patient in detail. Results of treatment of SPMS in advanced cases (Extended Disability Status Score greater than 6.5, or restricted to wheelchair) is mostly unknown. These patients are at high risk of developing infections, especially if they use indwelling catheters, and the use of agents that induce immunosuppression may be risky. There are no effective therapies for primary progressive multiple sclerosis (PPMS). Although PPMS patients are frequently treated with one or more therapeutic agents, there is no medical justification for this now.
authors.affiliation: Department of Neurology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, B183, Denver, CO 80262, USA. john.corboy@UCHSC.edu
authors.forename: John R.
authors.initials: JR
authors.lastname: Corboy
authors.forename: Douglas S.
authors.initials: DS
authors.lastname: Goodin
authors.forename: Elliot M.
authors.initials: EM
authors.lastname: Frohman