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The Canadian Multiple Sclerosis Working Group has updated its treatment optimization recommendations (TORs) on the optimal use of disease-modifying therapies for patients with all forms of multiple sclerosis (MS). Recommendations provide guidance on initiating effective treatment early in the course of disease, monitoring response to therapy, and modifying or switching therapies to optimize disease control. The current TORs also address the treatment of pediatric MS, progressive MS and the identification and treatment of aggressive forms of the disease. Newer therapies offer improved efficacy, but also have potential safety concerns that must be adequately balanced, notably when treatment sequencing is considered. There are added discussions regarding the management of pregnancy, the future potential of biomarkers and consideration as to when it may be prudent to stop therapy. These TORs are meant to be used and interpreted by all neurologists with a special interest in the management of MS.
This chapter summarizes interferon (IFN) biological effects, its possible mechanisms of action, and the key studies in clinically isolated syndromes (CIS), relapsing remitting multiple sclerosis (RRMS), and progressive MS. Measures of specific IFNβ-induced products, such as oligoadenylate synthetase (OAS), β-2 microglobulin, or neopterin, have been useful in pharmacodynamic studies to determine the magnitude and duration of the IFNβ-response, since serum levels of IFNβ are undetectable following injections. A consistent finding of follow-up studies from the three pivotal IFNβ RRMS trials and two CIS trials is that early treatment is beneficial compared with delayed treatment. IFNβ is partially effective in clinical trial groups. Since approval 18 years ago of the first IFNβ product for RRMS, treatment effects of β at all stages of MS have become fairly clear. The development of β for MS has illustrated many of the challenges in developing treatments for MS.
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