title: Prescribing recommendations for interferon-Beta in multiple sclerosis.
abstract: Multiple sclerosis (MS) is the most common cause of nontraumatic disability affecting young adults in temperate climates. Based on the concept of MS as a tissue-specific autoimmune disease, immunosuppression and immunomodulation have been the mainstays of therapeutic strategies. The rationale for using interferons (IFNs) to treat MS relies primarily on their immunoregulatory effects. Two phase III randomised, placebo-controlled clinical trials independently documented clinical and magnetic resonance imaging (MRI) evidence for the efficacy of IFNβ using similar but distinct products. As a result of these clinical studies, the US Food and Drug Administration (FDA) approved recombinant IFNβ-1b and, subsequently, recombinant IFNβ-1a for relapsing-remitting MS. IFNβ-1b is currently approved for use in almost all countries around the world, while IFNβ-1a has gained approval in Europe and Israel.IFNβ-1b is a nonglycosylated recombinant IFNβ expressed by Escherichia coli cells. It differs from the native human IFNβ by having a serine for cysteine substitution at position 17. IFNβ-1a is identical in terms of amino acid composition to native human IFNβ, is glycosylated, and is expressed by a mammalian cell line. IFNβ represents the first treatment approved by the US FDA to modify the natural course of MS. Ongoing studies of IFNβ for patients at first presentation with MS, and in chronic progressive MS, will clarify the role of IFNβ in the near future.Despite demonstrable efficacy in the setting of controlled clinical trials, important practice issues that require clarification include the magnitude of long term clinical benefits, toxicity of long term therapy, cost, and the relative value of therapy compared with symptomatic treatment, rehabilitation, education and support services. Because only partial therapeutic benefits have been demonstrated in short term clinical trials, long-range benefits and toxicities of IFNβ are largely undefined.Since the cost of therapy is high, it seems prudent to restrict the use of IFNβ to MS patients who are likely to benefit. This requires selection of patients based not only on their past and current disease type, but also on a determination of the likelihood of subsequent disease progression. Selection of patients for IFNβ therapy should therefore be performed by neurologists based on explicit criteria. Once selected, patients require adequate education about the goals, expectations and method of treatment, and support during the early months of treatment. These critical factors are important elements that promote patient compliance. Recommendations to deviate from the recommended dose usually relate to adverse effects, and many important MS-related issues must be managed during chronic IFNβ therapy. Therefore, periodic neurological reassessment is essential for appropriate management.
authors: The Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic Foundation, Cleveland, Ohio, 44195, USA, guttmab@cesmtp.ccf.org.
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authors: Weinstock-Guttman
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authors: Rudick