timing of high-efficacy disease modifying therapies for relapsing-remitting multiple sclerosis

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The study evaluated the effect of early treatment with high-efficacy disease modifying therapies (DMTs) on disease outcomes in relapsing-remitting multiple sclerosis (MS).


We have used the global MSBase cohort study to compare relapse and disability outcomes in patients who commenced (i) high-efficacy DMTs (alemtuzumab, natalizumab or fingolimod) versus low-efficacy DMTs within 4 years of their diagnosis of MS, or (ii) high-efficacy DMTs within 4 years versus after 6 years from diagnosis. Finally, we evaluated the association between the time of commencing therapy and the magnitude of the difference in disease outcomes between high-efficacy and low-efficacy DMTs. The study used propensity score matching with pairwise censoring to mitigate indication and attrition bias, intention-to-treat approach to mitigate the effect of informed censoring, analysis of robustness to unmeasured confounding and multiple sensitivity analyses.


430 and 1295 matched patients commenced high-efficacy or low-efficacy DMTs within 4 years of diagnosis, respectively. The patients treated early with high-efficacy DMTs experienced less relapses (annualised relapse rate 0.22 versus 0.42) and were more likely to recover from disability (hazard ratio 1.5, p=0.04) than those commencing low-efficacy DMTs. 619 and 1210 matched patients commenced high-efficacy DMTs within 4 years or after 6 years of their diagnosis, respectively. No differences in disease outcomes were observed. Finally, 500 and 1949 patients commenced high-efficacy or low-efficacy DMTs (irrespective of the date of commencement), respectively. The difference in annualised relapse rate between the high- and low-efficacy DMTs diminished with time. In contrast, no time-dependent flux in disability outcomes was observed.


Early commencement of high-efficacy DMTs in relapsing-remitting multiple sclerosis provides superior control over relapse activity than their delayed commencement. However, disability outcomes on high-efficacy DMTs are independent of the timing of therapy.

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