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) for MS patients with disabling relapses. For example, natalizumab and fingolimod can only be used first-line in case of rapidly evolving, severe MS, as Dr. Cyrus Daruwalla (Cambridge University Hospitals, UK) pointed out. Confronted with NDRs, a neurologist is uncertain about their prognostic significance and how they influence treatment. A study was initiated to determine whether NDRs early in the course of RRMS herald faster accumulation of disability than in the absence of such relapses and herald slower accumulation of disability than early disabling relapses.

Prospectively collected data was used from 78,531 patients 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 and were assigned to one of 3 groups: no treatment, treatment with 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).

Results of the primary analysis showed that 285 untreated RRMS patients who had NDRs, had a slightly increased risk of disability accumulation versus 4,717 patients with no relapses (HR=1.29; 95% CI 1.00–1.68). A total of 1,074 patients treated with platform DMTs who had NDRs, had a significantly increased risk of disability accumulation compared with 7,262 patients without relapses (HR=1.33; 95% CI 1.15–1.54). No difference was measured between 572 users of high-efficacy DMTS and 3,534 participants without relapses (HR 0.90; 95% CI 0.71–1.13).

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

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