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Drug Insight: interferon treatment in multiple sclerosis

Nature Clinical Practice Neurology volume 2, pages 34–44 (2006)Cite this article

Abstract

Multiple sclerosis (MS) is a chronic demyelinating disease of the CNS. Between 1987 and 1997, clinical trials of three preparations of recombinant interferon-β were conducted in patients with MS, ushering in a new therapeutic era. These medications have demonstrable benefits and seem to be safe; they represent an important advance in MS treatment. All three formulations of interferon-β had modest effects on relapses and short-term progression of disability, but the effects on MRI lesion parameters were more substantial. The benefits were greater in clinically isolated syndromes and relapsing–remitting MS than in secondary progressive MS. Although these drugs have been shown to be effective, however, their long-term impact on clinically relevant disability progression is uncertain, and there are many areas of controversy in the MS field regarding the use of these products. There is still a need for more effective treatments, which might include new agents or combination therapies.

Key Points

  • Interferons (IFNs) are naturally occurring proteins with antiviral, antiproliferative, antineoplastic and immunomodulatory actions

  • Between 1987 and 1997, clinical trials of three preparations of recombinant IFN-β were conducted in patients with multiple sclerosis (MS), ushering in a new therapeutic era

  • All three formulations of IFN-β have modest beneficial effects on relapses and short-term progression of disability; the effects on MRI lesion parameters are more substantial, but the clinical relevance of this finding remains unclear

  • The demonstrated benefit of IFN-β in mice with experimental autoimmune encephalomyelitis indicates that immunomodulatory or anti-inflammatory effects might be responsible for its therapeutic effects

  • Individuals treated with IFN-β can develop neutralizing antibodies to the medication that reduce its bioavailability, leading to reduced efficacy on relapse and MRI endpoints

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Figure 1: Randomized controlled trials of interferon-β in multiple sclerosis: rate ratios and 95% CIs for annual relapse rates for highest dose studied.
Figure 2: Randomized controlled trials of interferon-β in relapsing–remitting multiple sclerosis: percent change in T2-lesion burden at 2 years.
Figure 3: Randomized controlled trials of interferon-β in secondary progressive multiple sclerosis: percent change in T2-lesion burden.

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Acknowledgements

This study was supported in part by the National Institutes of Health, National Institute of Child Health and Human Development, Multidisciplinary Clinical Research Career Development Programs Grant K12 HD049091.

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Authors and Affiliations

  1. Mellen Center for Multiple Sclerosis Treatment and Research,

    Ruth Ann Marrie & Richard A Rudick

  2. Director of the Mellen Center,

    Ruth Ann Marrie & Richard A Rudick

  3. Chairman of the Division of Clinical Research at the Cleveland Clinic Foundation, Cleveland, OH, USA

    Ruth Ann Marrie & Richard A Rudick

Authors
  1. Ruth Ann Marrie
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  2. Richard A Rudick
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Corresponding author

Correspondence to Ruth Ann Marrie.

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Competing interests

Dr Rudick has received within the past 3 years honoraria for advisory panels or speaking from Biogen Idec, Teva, Vertex, Millenium, and the American Academy of Neurology. Dr Rudick was an investigator in the MSCRG study of Avonex discussed in this review. That study was sponsored by NIH (NINDS) and by Biogen, Inc. Dr Rudick's current research is supported by the National Institutes of Health (NINDS, NICHD, and NCRR), the National Multiple Sclerosis Society, the Nancy Davis Foundation, and Biogen Idec. Dr Rudick has no equity or ownership positions in any company related to this review.

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Marrie, R., Rudick, R. Drug Insight: interferon treatment in multiple sclerosis. Nat Rev Neurol 2, 34–44 (2006). https://doi.org/10.1038/ncpneuro0088

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