Patients with multiple sclerosis (MS) typically present with a clinically isolated syndrome (CIS), which eventually develops into relapsing– remitting MS (RRMS); after a varying number of years, most patients transform into secondary progressive MS (SPMS). An alternative course is primary progressive MS (PPMS), which develops more rapidly from onset and is also inevitably accompanied by some decline in walking ability.¹ In early MS, the prognosis after disease onset is highly variable and the time taken to progress to irreversible disability is generally unpredictable.

A number of studies have shown that disease onset in later life generally results in more rapid progression. This was shown in a study of 1,844 patients with MS in France, which found that individuals who were diagnosed with MS at up to 29 years of age took a median of 33 years to progress to a disability status score of 7 (unable to walk more than 10m without rest and/or support), whereas in patients diagnosed at over 50 years of age, a similar progression was seen in a median of only 17 years (see Figure 1).² In the same study, progression from RRMS to SPMS was estimated to occur in about 2.5% of patients per year and the median time to conversion was 19.1 years.³ These findings also indicate that increasing disability in MS occurs at widely varying rates, but it is inevitable that over periods of many years, the abilities ofpatients will decline and they will require increasing levels of support.

Most clinical trials and studies of patients with MS have focused on RRMS. As a consequence, there is a large body of information available on this phase of the disease, but less on progression and disability during later stages of MS. This deficiency needs to be addressed. In SPMS, disability is more apparent, severely restricting the functions and activities of patients, and it is more difficult to treat than at earlier phases of the disease. Interventions designed to stop or more effectively delay progression of disability in MS are a substantial unmet clinical need.

The currently available treatments for MS are targeted primarily at reducing inflammation, and have been shown to reduce relapse rates and pathological activity as detected by magnetic resonance imaging (MRI). However, these treatments are not sufficient on their own, as they do not address decreasing axonal function.4 Managing MS must therefore also involve managing the symptoms of disease progression, in particular limitations of activities and social participation, an area of research that continues to require development.^4–7

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