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002 Therapeutic lag in relapsing multiple sclerosis
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  1. Izanne Roos1,2,
  2. Federico Frascoli3,
  3. Jeannette Lechner-Scott4,5,
  4. Pamela McCombe6,
  5. Richard Macdonell7,8,
  6. Helmut Butzkueven2,9,10,
  7. Charles Malpas1,
  8. Tomas Kalincik1,2
  1. 1CORe Unit, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia
  2. 2Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia
  3. 3Department of Mathematics, Swinburne University of Technology, Faculty of Science, Engineering and Technology, Melbourne, VIC, Australia
  4. 4School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
  5. 5Department of Neurology, John Hunter Hospital, Hunter New England Health, Newcastle, NSW, Australia
  6. 6Department of Neurology, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia
  7. 7Department of Neurology, Austin Health, Melbourne, VIC, Australia
  8. 8Florey Institute of Neuroscience, Melbourne, VIC, Australia
  9. 9Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia
  10. 10Department of Neurology, Alfred Hospital, Melbourne, VIC, Australia

Abstract

Introduction In multiple sclerosis (MS), treatment start or switch is prompted disease activity, often represented by relapses. Immunomodulatory therapies have potent effects on relapse rates but the time required to attain maximal effect is unclear. We aim to develop a method that allows identification of the time to full clinically manifest effect of treatment on relapses.

Methods Data from MSBase, a multinational MS registry, were used. Inclusion criteria consisted of patients with remitting relapsing MS or clinically isolated syndrome (CIS), minimum 3-year pre-treatment follow up, 1-year treatment persistence, yearly review and availability of the minimum dataset. Stratified by therapy, density curves representing relapses occurrence were created. The first local minimum of the first derivative after treatment start was identified, representing stabilisation of treatment effect. Similar method was utilised to calculate the last pre-treatment point of stabilisation. Annualised relapse rates (ARR) were compared in the pre-treatment pre stabilisation and post-treatment post stabilisation periods.

Results 4979 eligible patients with 6218 treatment epochs were identified for analysis. Time, in years, to treatment effect was shortest for interferon beta-1a sc (0.22, 0.19–0.22), interferon beta-1b (0.24, 0.21–0.24) and fingolimod (0.26, 0.23–0.26) and longest for dimethyl fumarate (0.54, 0.51–0.54) and glatiramer acetate (0.62, 0.60–0.62). Significant differences in pre vs post treatment ARR were present for patients on natalizumab, fingolimod and dimethyl fumarate. A sequential analysis confirmed outcome stability after approximately 1000 recorded number of events.

Conclusions We have developed a method to objectively quantify time from commencing therapy to its full effect. Time to full effect varies among therapies.

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