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008 Disease reactivation after cessation of disease-modifying therapy in relapsing-remitting multiple sclerosis
  1. Izanne Roos1,2,
  2. Charles B Malpas1,2,
  3. Emmanuelle Leray3,
  4. Katherine Buzzard2,4,
  5. Olga Skibina4,5,
  6. Jeannette Lechner-Scott6,7,
  7. Pamela McCombe8,
  8. Mark Slee9,
  9. Ernest Butler10,
  10. Richard Macdonell11,
  11. Anneke van der Walt5,12,
  12. Suzanne Hodgkinson13,
  13. Michael Barnett14,
  14. Steve Vucic15,
  15. Sandra Vukusic16,
  16. Helmut Butzkueven5,12 and
  17. 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. 3Rennes University, Rennes, France
  4. 4Department of Neurology, Box Hill Hospital, Monash University, Melbourne, VIC, Australia
  5. 5Department of Neurology, The Alfred Hospital, Melbourne, VIC, Australia
  6. 6School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
  7. 7Department of Neurology, John Hunter Hospital, Hunter New England Health, Newcastle, NSW, Australia
  8. 8Department of Neurology, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia
  9. 9Flinders University, Adelaide, SA, Australia
  10. 10Monash Medical Centre, Melbourne, VIC, Australia
  11. 11Department of Neurology, Austin Health, Melbourne, VIC, Australia
  12. 12Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia
  13. 13Liverpool Hospital, Sydney, NSW, Australia
  14. 14Brain and Mind Centre, Sydney, NSW, Australia
  15. 15Westmead Hospital, Sydney, NSW, Australia
  16. 16Hospital Neurologique Pierre Wertheimer, Lyon, France


Objectives To evaluate the rate of return of disease activity after cessation of multiple sclerosis (MS) disease-modifying therapy.

Methods This was a retrospective cohort study from two large observational MS registries: MSBase and OFSEP. Patients with relapsing-remitting MS who had ceased a disease-modifying therapy and were followed up for the subsequent 12-months were included in the analysis. The primary study outcome was annualised relapse rate in the 12 months after disease-modifying therapy discontinuation stratified by patients who did, and did not, commence a subsequent therapy. The secondary endpoint was the predictors of first relapse and disability accumulation after treatment discontinuation.

Results 18 029 eligible treatment discontinuation epochs were identified for seven therapies. Rates of relapse started to increase 2-months after natalizumab cessation. Commencement of a subsequent therapy within 2-4 months reduced the magnitude of disease reactivation. After discontinuation of fingolimod, rates of relapse increased overall, and stabilised faster in patients who started a new therapy within 1-2 months. Magnitude of disease reactivation for other therapies was low, but reduced further by commencement of another treatment 1-10 months after treatment discontinuation. Predictors of relapse were higher relapse rate in the year before cessation, female sex, younger age and higher EDSS. Commencement of a subsequent therapy reduced both the risk of relapse (HR 0.76, CI 0.72-0.81) and disability accumulation (0.73, 0.65-0.80).

Conclusion Understanding the rate of disease reactivation after discontinuing different MS immunotherapies will help guide optimal wash-out times for therapeutic agents during treatment sequencing.

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