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Discontinuation of disease-modifying treatments for multiple sclerosis in patients aged over 50 with disease Inactivity

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Abstract

Background

Treatments may become redundant in older patients with multiple sclerosis (MS). Our aim was to explore whether stopping treatments might be possible in patients aged over 50 with disease inactivity.

Methods

Patients over 50 were included from the population-based MS Lorraine registry if they had a relapsing–remitting course at onset and had experienced no relapse for ≥ 3 years. Patients who stopped treatments were defined as “stoppers”, and the others as “stayers”. The outcomes were the time to first relapse, to first disability progression, and to the occurrence of EDSS score of 6, assessed by multivariate analysis using a propensity score.

Results

132 stoppers and 366 stayers had a median follow-up of 7 years. There was no difference in Log-rank tests for the times to first relapse (p = 0.61) and to first disability progression (p = 0.22). In Cox models, stopping treatments was not associated with an increased risk of relapse (adjusted Hazard ratio (aHR) = 0.92 [0.72–1.16; p = 0.47]) or of an increase in EDSS score (aHR = 0.89 [0.71–1.13; p = 0.34]). However, stopping was associated with a higher risk of occurrence of EDSS score of 6 (aHR = 3.29 [2.22–4.86; p < 0.0001]), with a significant difference for the time to occurrence of EDSS score of 6 (p = 0.003).

Conclusion

Our study suggests that stopping injectable disease-modifying treatments, in patients over 50 with disease inactivity, is not associated with an increased risk of relapse or EDSS progression, but there might be a higher risk of reaching EDSS 6. These results have to be confirmed by interventional studies.

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References

  1. Rotstein DL, Healy BC, Malik MT et al (2015) Evaluation of No Evidence of Disease Activity in a 7-Year Longitudinal Multiple Sclerosis Cohort. JAMA Neurol 72:152–158. https://doi.org/10.1001/jamaneurol.2014.3537

    Article  PubMed  Google Scholar 

  2. Tremlett H, Zhao Y, Joseph J et al (2008) Relapses in multiple sclerosis are age- and time-dependent. J Neurol Neurosurg Psychiatry 79:1368–1374. https://doi.org/10.1136/jnnp.2008.145805

    Article  CAS  PubMed  Google Scholar 

  3. Frischer JM, Bramow S, Dal-Bianco A et al (2009) The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain 132:1175–1189. https://doi.org/10.1093/brain/awp070

    Article  PubMed  PubMed Central  Google Scholar 

  4. Paz Soldán MM, Novotna M, Abou Zeid N et al (2015) Relapses and disability accumulation in progressive multiple sclerosis. Neurology 84:81–88. https://doi.org/10.1212/WNL.0000000000001094

    Article  PubMed  PubMed Central  Google Scholar 

  5. Grebenciucova E, Pruitt A (2017) Infections in patients receiving multiple sclerosis disease-modifying therapies. Curr Neurol Neurosci Rep 17:88. https://doi.org/10.1007/s11910-017-0800-8

    Article  PubMed  Google Scholar 

  6. Reder AT, Oger JF, Kappos L et al (2014) Short-term and long-term safety and tolerability of interferon β-1b in multiple sclerosis. Multiple Sclerosis and Related Disorders 3:294–302. https://doi.org/10.1016/j.msard.2013.11.005

    Article  PubMed  Google Scholar 

  7. Secondary Progressive Efficacy Clinical Trial of Recombinant Interferon-Beta-1a in MS (SPECTRIMS) Study Group (2001) Randomized controlled trial of interferon- beta-1a in secondary progressive MS: clinical results. Neurology 56:1496–1504

    Article  Google Scholar 

  8. Andersen O, Elovaara I, Färkkilä M et al (2004) Multicentre, randomised, double blind, placebo controlled, phase III study of weekly, low dose, subcutaneous interferon beta-1a in secondary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 75:706–710

    Article  CAS  Google Scholar 

  9. Panitch H, Miller A, Paty D et al (2004) Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study. Neurology 63:1788–1795

    Article  Google Scholar 

  10. Cohen JA, Cutter GR, Fischer JS et al (2002) Benefit of interferon beta-1a on MSFC progression in secondary progressive MS. Neurology 59:679–687

    Article  CAS  Google Scholar 

  11. Bonenfant J, Bajeux E, Deburghgraeve V et al (2017) Can we stop immunomodulatory treatments in secondary progressive multiple sclerosis? Eur J Neurol 24:237–244. https://doi.org/10.1111/ene.13181

    Article  CAS  PubMed  Google Scholar 

  12. Do Olival GS, Cavenaghi VB, Serafim V et al (2013) Medication withdrawal may be an option for a select group of patients in relapsing-remitting multiple sclerosis. Arq Neuropsiquiatr 71:516–520. https://doi.org/10.1590/0004-282X20130081

    Article  Google Scholar 

  13. Siger M, Durko A, Nicpan A et al (2011) Discontinuation of interferon beta therapy in multiple sclerosis patients with high pre-treatment disease activity leads to prompt return to previous disease activity. J Neurol Sci 303:50–52. https://doi.org/10.1016/j.jns.2011.01.016

    Article  PubMed  Google Scholar 

  14. Prosperini L, Mancinelli CR, Pozzilli C et al (2014) From high- to low-frequency administered interferon-beta for multiple sclerosis: a multicenter study. Eur Neurol 71:233–241. https://doi.org/10.1159/000356786

    Article  CAS  PubMed  Google Scholar 

  15. Wu X, Dastidar P, Kuusisto H et al (2005) Increased disability and MRI lesions after discontinuation of IFN-beta-1a in secondary progressive MS. Acta Neurol Scand 112:242–247. https://doi.org/10.1111/j.1600-0404.2005.00477.x

    Article  CAS  PubMed  Google Scholar 

  16. Fox RJ, Cree BA, De Sèze J et al (2014) MS disease activity in RESTORE: a randomized 24-week natalizumab treatment interruption study. Neurology 82:1491–1498. https://doi.org/10.1212/WNL.0000000000000355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kister I, Spelman T, Alroughani R et al (2016) Discontinuing disease-modifying therapy in MS after a prolonged relapse-free period: a propensity score-matched study. J Neurol Neurosurg Psychiatry 87:1133–1137. https://doi.org/10.1136/jnnp-2016-313760

    Article  PubMed  Google Scholar 

  18. Debouverie M, Pittion-Vouyovitch S, Louis S et al (2008) Natural history of multiple sclerosis in a population-based cohort. Eur J Neurol 15:916–921. https://doi.org/10.1111/j.1468-1331.2008.02241.x

    Article  CAS  PubMed  Google Scholar 

  19. El Adssi H, Debouverie M, Guillemin F et al (2012) Estimating the prevalence and incidence of multiple sclerosis in the Lorraine region, France, by the capture-recapture method. Multiple Sclerosis Journal 18:1244–1250. https://doi.org/10.1177/1352458512437811

    Article  PubMed  Google Scholar 

  20. Confavreux C, Compston DA, Hommes OR et al (1992) EDMUS, a European database for multiple sclerosis. J Neurol Neurosurg Psychiatry 55:671–676

    Article  CAS  Google Scholar 

  21. Poser CM, Paty DW, Scheinberg L et al (1983) New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 13:227–231. https://doi.org/10.1002/ana.410130302

    Article  CAS  PubMed  Google Scholar 

  22. McDonald WI, Compston A, Edan G et al (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 50:121–127

    Article  CAS  Google Scholar 

  23. Polman CH, Reingold SC, Edan G et al (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol 58:840–846

    Article  Google Scholar 

  24. Polman CH, Reingold SC, Banwell B et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292–302. https://doi.org/10.1002/ana.22366

    Article  PubMed  PubMed Central  Google Scholar 

  25. Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452

    Article  CAS  Google Scholar 

  26. Austin PC, Stuart EA (2015) Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med 34(28):3661–3679. https://doi.org/10.1002/sim.6607

    Article  PubMed  PubMed Central  Google Scholar 

  27. Deb S, Austin PC, Tu JV et al (2016) A review of propensity-score methods and their use in cardiovascular research. Can J Cardiol 32(2):259–265. https://doi.org/10.1016/j.cjca.2015.05.015

    Article  PubMed  Google Scholar 

  28. Hua LH, Fan TH, Conway D et al (2018) Discontinuation of disease-modifying therapy in patients with multiple sclerosis over age 60. Multiple Sclerosis. https://doi.org/10.1177/1352458518765656

    Article  PubMed  Google Scholar 

  29. Birnbaum G (2017) Stopping disease-modifying therapy in nonrelapsing multiple sclerosis. Int J MS Care 19:11–14. https://doi.org/10.7224/1537-2073.2015-032

    Article  PubMed  PubMed Central  Google Scholar 

  30. Tremlett H, Zhao Y, Devonshire V (2008) Natural history of secondary-progressive multiple sclerosis. Multiple Sclerosis 14:314–324. https://doi.org/10.1177/1352458507084264

    Article  PubMed  Google Scholar 

  31. Fagius J, Feresiadou A, Larsson EM et al (2017) Discontinuation of disease modifying treatments in middle aged multiple sclerosis patients. First line drugs vs natalizumab. Multiple Sclerosis Related Disord 12:82–87. https://doi.org/10.1016/j.msard.2017.01.009

    Article  Google Scholar 

  32. Sorensen PS, Koch-Henriksen N, Petersen T, Ravnborg M, Oturai A, Sellebjerg F (2014) Recurrence or rebound of clinical relapses after discontinuation of natalizumab therapy in highly active MS patients. J Neurol 261:1170–1177. https://doi.org/10.1007/s00415-014-7325-8

    Article  CAS  PubMed  Google Scholar 

  33. Rae-Grant A, Day GS, Marrie RA et al (2018) Practice Guideline Recommendations Summary: disease-modifying Therapies for adults with multiple sclerosis: report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology. Neurology 90(17):777–788. https://doi.org/10.1212/wnl.0000000000005347

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank the patients and the research technicians for their contributions. The authors thank Felicity Neilson (Matrix Consultants) for medical English editing services.

Funding

This research received no specific Grant from any funding agency in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Neurology, University Hospital of Nancy, 29 avenue Maréchal de Lattre de Tassigny, 60034–54035, Nancy, CO, France

    Anne-Laure Kaminsky, Sophie Pittion-Vouyovitch, Maud Michaud, Marc Debouverie & Guillaume Mathey

  2. Inserm, CIC-1433 Clinical Epidemiology, University Hospital of Nancy, Université de Lorraine, Vandœuvre-Lès-Nancy, France

    Abdou Yacoubou Omorou, Marc Soudant & Francis Guillemin

  3. Department of Diagnostic and Therapeutic Neuroradiology, University Hospital of Nancy, Nancy, France

    René Anxionnat

Authors
  1. Anne-Laure Kaminsky
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  2. Abdou Yacoubou Omorou
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  3. Marc Soudant
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  4. Sophie Pittion-Vouyovitch
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  5. Maud Michaud
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  6. René Anxionnat
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  7. Francis Guillemin
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  8. Marc Debouverie
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  9. Guillaume Mathey
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Marc Soudant, Abdou Yacoubou Omorou, Guillaume Mathey and Anne-Laure Kaminsky. The first draft of the manuscript was written by Anne-Laure Kaminsky and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Anne-Laure Kaminsky.

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Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethics approval

The data collection for this study was approved by the French National Commission for Data Protection and Liberties (CNIL n° 8493536 and 8493536 bis).

Consent to participate and consent for publication

All the patients were informed that their data were recorded and that they may be used for research purposes according to the French Law concerning non-interventional research.

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Kaminsky, AL., Omorou, A.Y., Soudant, M. et al. Discontinuation of disease-modifying treatments for multiple sclerosis in patients aged over 50 with disease Inactivity. J Neurol 267, 3518–3527 (2020). https://doi.org/10.1007/s00415-020-10029-9

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  • DOI: https://doi.org/10.1007/s00415-020-10029-9

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