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Early, non-disabling relapses increase disability accumulation

Presented by
Dr Cyrus Daruwalla, Cambridge University Hospitals, UK

Non-disabling relapses (NDRs) that occur early in the course of relapsing-remitting MS (RRMS) are associated with a higher risk of disability accumulation. These types of relapses should therefore be taken into consideration when making treatment decisions, as was concluded from a prospective registry study.

The European Medicines Agency (EMA) restricts the use of certain disease-modifying treatments (DMTs) to MS patients with disabling relapses. For example, natalizumab and fingolimod can only be used in the first line in case of rapidly-evolving, severe MS, Dr Cyrus Daruwalla (Cambridge University Hospitals, UK) pointed out. Confronted with NDRs, a neurologist is uncertain about the prognostic significance and whether the NDRs should influence treatment. A study set out to determine whether NDRs early in the course of RRMS herald faster accumulation of disability than the absence of such relapses [1].

Prospectively-collected data was used from 78,531 participants from the MSBase international registry (msbase.org). Participants with NDRs only were compared with those with no relapses in the first 2 years after attaining clinically definite RRMS. To mitigate the confounding effect of DMTs, participants were stratified according to the highest-efficacy DMT they received during follow-up into no treatment, platform therapies, or high-efficacy DMT. For each group was assessed whether early NDRs were associated with 90-day confirmed disability accumulation events, defined as an increase in Expanded Disability Status Scale (EDSS) score of 1.0 (or 1.5 if the baseline EDSS=0, or 0.5 if the baseline EDSS>5).

Untreated RRMS participants with NDRs had a significantly higher risk of disability accumulation (+29%) than participants with no relapses (see Figure). Participants treated with platform DMTs who had NDRs, had a significantly increased risk of disability accumulation compared with participants without relapses. No difference was detected between users of high-efficacy DMTs and participants without relapses.

Figure: Disability accumulation for no treatment, platform therapies, or high-efficacy DMT [1]

DMT, disease-modifying treatments; RRMS, relapsing-remitting MS.

“Contrary to EMA guidance, NDRs should be considered in decisions to initiate or escalate treatment, including high-efficacy therapies,” concluded Dr Daruwalla.

  1. Daruwalla C, et al. Early non-disabling relapses are associated with a higher risk of disability accumulation in people with relapsing-remitting multiple sclerosis. Abstract O178, ECTRIMS 2022, 26–28 October, Amsterdam, the Netherlands.

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