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timing of high-efficacy disease modifying therapies for relapsing-remitting multiple sclerosis
  1. Bernd Merkel1,
  2. Vilija Jokubaitis1,
  3. Tim Spelman2,
  4. Jeannette Lechner-Scott3,
  5. Pamela McCombe4,
  6. Mark Slee5,
  7. Steve Vucic6,
  8. Olga Skibina7,
  9. Michael Barnett8,
  10. Suzanne Hodgkinson9,
  11. Helmut Butzkueven1,
  12. Tomas Kalincik1
  1. 1University of Melbourne, Melbourne, Australia
  2. 2Royal Melbourne Hospital, Melbourne, VIC, Australia
  3. 3University Newcastle, Newcastle, NSW, Australia
  4. 4University of Queensland, Brisbane, QLD, Australia
  5. 5Flinders University, Adelaide, SA, Australia
  6. 6Westmead Hospital, Sydney, NSW, Australia
  7. 7The Alfred, Melbourne, VIC, Australia
  8. 8University of Sydney, Sydney, NSW, Australia
  9. 9Liverpool Hospital, Sydney, NSW, Australia


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.

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