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Original research
Rebound of clinical disease activity after fingolimod discontinuation? A nationwide cohort study of patients in Denmark
  1. Elisabeth Framke1,
  2. Luigi Pontieri1,
  3. Stephan Bramow2,
  4. Finn Sellebjerg2,3,
  5. Melinda Magyari1,2,3
  1. 1 The Danish Multiple Sclerosis Registry, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark
  2. 2 Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital – Rigshospitalet, Glostrup, Denmark
  3. 3 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  1. Correspondence to Dr Elisabeth Framke, The Danish Multiple Sclerosis Registry, Copenhagen University Hospital Danish Multiple Sclerosis Research Center, Glostrup, DK-2600, Denmark; elisabeth.framke{at}regionh.dk

Abstract

Objective We investigated whether clinical rebound occurred after fingolimod discontinuation in a complete population of patients with relapsing-remitting multiple sclerosis (RRMS) in Denmark. We further identified clinical and demographical factors associated with disease reactivation after fingolimod discontinuation.

Methods The population comprised 992 RRMS patients treated with fingolimod for 6 months or more. We estimated annualised relapse rates (ARR) before, during and after treatment. We estimated overall ARRs and ARRs stratified by disease activity before discontinuation. We calculated the proportion of patients with a higher clinical disease activity after discontinuation than before treatment start. Finally, we analysed the association between variables at discontinuation and time to first relapse after discontinuation.

Results The ARR 3 months after discontinuation (ARR=0.56; 95% CI=0.47 to 0.66) was statistically significantly lower (p<0.01) than the ARR 1 year before treatment (ARR=0.74; 95% CI=0.69 to 0.80). Results were similar when repeating analyses in patients with and without disease activity before discontinuation. In total, 124 patients (12.5%) had clinical rebound. Of those, 36 had no disease breakthrough before discontinuation (3.6% of total population). On treatment disease activity (HR=1.98, p<0.01), lower age (HR=0.98, p=0.01) and female sex (HR=1.68, p=0.02) were associated with a higher relapse risk after discontinuation.

Conclusions Based on average ARR levels, there was no evidence of clinical rebound after fingolimod discontinuation. In total, 12.5% of patients had clinical rebound. Only 3.6%, however, had clinical rebound without disease activity before discontinuation. Disease activity before discontinuation, female sex and younger age were statistically significantly associated with a higher relapse risk after discontinuation.

  • MULTIPLE SCLEROSIS
  • NEUROIMMUNOLOGY

Data availability statement

Data are available upon reasonable request. All data relevant to the study is included in the article. The data underlying this article cannot be shared publicly due to data protection regulation. Data is accessible to authorised researchers after application to the Danish Health Data Authority and the board of the Danish Multiple Sclerosis Registry.

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Data availability statement

Data are available upon reasonable request. All data relevant to the study is included in the article. The data underlying this article cannot be shared publicly due to data protection regulation. Data is accessible to authorised researchers after application to the Danish Health Data Authority and the board of the Danish Multiple Sclerosis Registry.

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Footnotes

  • Contributors Conception or design of the work: EF, MM and FS. Acquisition, analysis or interpretation of data for the work: EF, MM, FS, SB and LP. Drafting the work and revising it critically for important intellectual content and final approval: EF, MM, FS, SB and LP. Authors responsible for the overall content as guarantor: EF and MM.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests SB has received honoraria for advisory board activities from Biogen and Novartis. FS has served on scientific advisory boards for, served as consultant for, received support for congress participation or received speaker honoraria from Alexion, Biogen, Bristol Myers Squibb, Merck, Novartis, Roche and Sanofi Genzyme. His laboratory has received research support from Biogen, Merck, Novartis, Roche and Sanofi Genzyme. MM has served in scientific advisory board for Sanofi, Novartis, Merck, and has received honoraria for lecturing from Biogen, Merck, Novartis, Roche, Genzyme, Bristol Myers Squibb.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.