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Patients with MS demonstrate an accumulation of disabilities, which can be delayed by applying disease-modifying therapies.

Multiple sclerosis (MS) patients acquire disability via progression independent of relapse activity (PIRA) or relapse-associated worsening (RAW). This study was published in the journal BRAIN, and discusses the contribution of MS relapses to the worsening of disability through the course of MS. The study also discusses the early progression of MS and disability and how therapies can delay the accumulation of disabilities.

The authors utilized the Novartis-Oxford multiple sclerosis (NO.MS) data pools to evaluate approximately 200,000 Expanded Disability Status Scale (EDSS) transitions with a follow-up of ≤ 15 years and ≥ 27,000 patients. This study analyzed three subsets, including phase 3 placebo-controlled clinical trials, full analysis dataset, and all phase 3 clinical trials.

The authors used Andersen-Gill models for investigating the role of MS relapses in the worsening of all-cause disability, Markov models for observing the impact of therapies on the duration of reaching milestone disability levels, and also assessed the relative importance of PIRA and RAW. PIRA occurred early during the course of MS, in all phenotypes, and mediated accumulation of disability in the progressive phase of MS. The hazard associated with all-cause disability increased during the next year with the occurrence of relapses.

Older age and pre-existing disability comprise principal risk factors associated with incomplete relapse recovery. In placebo with minimal disability and EDSS 1, the duration for limitation in walking ability and the requirement for walking assistance was estimated to be 8.95 years (EDSS4) and 18.48 years (EDSS6), respectively.
The use of disease-modifying therapies increased the above-mentioned duration by 3.51 years and 3.09 years, respectively. A similar length of time was observed in RAW events in patients suffering from relapsing-remitting MS. The transitions were fastest among individuals with PIRA and superimposed MS relapses. The most frequently used therapies included glatiramer acetate, interferon beta-1a, fingolimod, natalizumab, ofatumumab, siponimod, dimethyl fumarate and teriflunomide.

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This study suggests that relapses mediate disability accumulation early in MS. PIRA initiates in relapsing-remitting MS, becoming a dominant aspect of disability as the disease progresses.

Reference
Lublin, F. D., Häring, D. A., Ganjgahi, H., Ocampo, A., Hatami, F., Čuklina, J., . . . Bermel, R. A. (2022). How patients with multiple sclerosis acquire disability. Brain, 145(9), 3147-3161. https://doi.org/10.1093/brain/awac016