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Current Treatments for Progressive Multiple Sclerosis: Disease-Modifying Therapies

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Progressive Multiple Sclerosis

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Abstract

The success of the phase III randomized controlled trials (RCTs) of disease-modifying therapies (DMTs) in relapsing–remitting multiple sclerosis (RRMS) naturally led to exploration of their efficacy in both secondary progressive multiple sclerosis (SPMS) and primary progressive multiple sclerosis (PPMS). Overall, apart from two RCTs in SPMS, the primary endpoints in these trials were not achieved. However, many secondary endpoints, for instance markers of inflammatory disease activity, demonstrated a marked treatment effect. Despite their negative outcomes, the trials described in this chapter have informed the MS research community about the natural history of progressive MS, and have stimulated both expert consensus diagnostic criteria and a search for new disability measures. Recognition of the limitations of the most commonly used measure of disability progression, the Expanded Disability Status Scale (EDSS) led to the development of other instruments, notably the Multiple Sclerosis Functional Composite (MSFC). The SPMS and PPMS trials have also contributed to the debate about the nature of the degenerative process in MS: is neurodegeneration in MS a separate primary disorder or simply secondary to an inflammatory process?

The practical and ethical constraints of placebo-controlled trials in MS have been discussed elsewhere. As in all RCTs of 2–3 years duration, there is a problem with the implied extrapolation of any demonstrated short-term efficacy to a lifelong illness. Apart from an effect on markers of inflammation, it should be recognized that, given the generally negative primary outcome measure of confirmed disability progression, there is no suggestion that presently discussed therapies are effective in altering long-term outcome in SPMS or PPMS.

The author will attempt to be scientifically dispassionate and try to indicate how these trials may help us to address treatment issues in this perplexing disease. The SPMS trials will be presented initially, partly because they were first to be undertaken.

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  1. Department of Neurology, St Vincent’s University Hospital, University College Dublin, Elm Park, Dublin 4, Ireland

    Michael Hutchinson B.Sc., M.B., FRCP, FRCPI

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  1. , Department of Neurology, Frenchay Hospital, Frenchay Park Road, Bristol, BS16 1LE, United Kingdom

    Alastair Wilkins

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Hutchinson, M. (2013). Current Treatments for Progressive Multiple Sclerosis: Disease-Modifying Therapies. In: Wilkins, A. (eds) Progressive Multiple Sclerosis. Springer, London. https://doi.org/10.1007/978-1-4471-2395-8_9

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