Timing of high-efficacy disease modifying therapies for relapsing-remitting multiple sclerosis. Issue 5 (8th May 2017)

• Record Type: Journal Article
• Authors: Merkel, Bernd; Jokubaitis, Vilija; Spelman, Tim; Lechner-Scott, Jeannette; McCombe, Pamela; Slee, Mark; Vucic, Steve; Skibina, Olga; Barnett, Michael; Hodgkinson, Suzanne; Butzkueven, Helmut; Kalincik, Tomas
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 88:Issue 5(2017)
• Page Start: e1
• Page End: e1
• Publication Date: 2017-05-08
• Subjects: Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2017-316074.16
• Languages: English
• ISSNs: 0022-3050

Abstract

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