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  • Review Article
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Clinical prognostic factors in multiple sclerosis: a natural history review

Nature Reviews Neurology volume 5, pages 672–682 (2009)Cite this article

Abstract

This Review summarizes the natural history studies on multiple sclerosis (MS) that have evaluated prognostic factors. Reassessment of prognostic factors is warranted, as our ability to offer patients a reliable prognosis is limited, yet we rely on this knowledge to appropriately design clinical trials and interpret their results. The selection criteria for studies to review included a geographical referral base, duration of at least 9 years, prospective design, and populations of at least 100 patients with MS. For all forms of MS combined, negative prognostic factors included progressive disease, and disability at 2 and 5 years. In relapsing–remitting MS (RRMS) and secondary progressive MS (SPMS) combined, negative prognostic factors were the onset of progression, a higher relapse rate, greater disability in the first 5 years, a shorter interval to the second relapse, and the involvement of more systems. Additional negative factors include a shorter time to progression in SPMS and a faster rate of disability in the first 2 and 5 years in primary progressive MS (PPMS). Onset of progression, relapse rate and disability in the initial 5 years could be fruitful therapeutic targets; however, longer-term clinical trials will be required to justify these end points.

Key Points

  • Natural history studies in multiple sclerosis (MS) identify factors associated with disability that are helpful in guiding prognosis; however, these factors are limited by the large variability in patient outcomes

  • Notable negative prognostic factors for MS in general include the onset of progressive disease, and disability at 2 and 5 years

  • In relapsing–remitting MS, negative prognostic factors included a higher relapse rate, a shorter interval to the second relapse, higher level of disability in the first 5 years, and the involvement of more systems

  • In secondary progressive MS, negative prognostic factors included a shorter time to progression

  • In primary progressive MS, negative prognostic factors included a faster rate to disability in the first 2 and 5 years, and the involvement of more than three systems

  • The presence of prognostic factors does not necessarily lead directly to disability, and when used in clinical trials as end points, such factors need to be assessed with long-term disability outcomes

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Figure 1
Figure 2: Median times to disability in patients with MS.

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  1. Department of Clinical Neurology, University of Oxford, Oxford, UK

    Alexandra Degenhardt, Sreeram V. Ramagopalan, Antonio Scalfari & George C. Ebers

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Natural history studies of multiple sclerosis: general characteristics (DOC 189 kb)

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Degenhardt, A., Ramagopalan, S., Scalfari, A. et al. Clinical prognostic factors in multiple sclerosis: a natural history review. Nat Rev Neurol 5, 672–682 (2009). https://doi.org/10.1038/nrneurol.2009.178

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