For older adults with relapsing-onset multiple sclerosis (MS), limited information is available to inform if, or when, disease-modifying drugs (DMDs) may be safely discontinued.
The aim of this study was to project the outcomes of DMD discontinuation among older adults with relapsing-onset MS.
We projected the 10-year outcomes of discontinuation of a DMD (interferon-β, fingolimod, or natalizumab) among older adults (aged 55 or 70 years) who were relapse-free for 5 or more years and had not reached an Expanded Disability Status Scale (EDSS) score of 6. Outcomes included the percentage of people who had at least one relapse or reached EDSS 6, and quality-adjusted life-years (QALYs), which incorporated both relapses and disability. We used a simulation modeling approach. With increased age, relapses decreased and the effectiveness of DMDs for disability outcomes also decreased.
We found lower projected benefits for DMD continuation at 70 years of age than at 55 years of age. Compared with discontinuation, the projected benefit of DMD continuation ranged from 0.007 to 0.017 QALYs at 55 years of age and dropped to 0.002–0.006 at 70 years of age. The annual projected benefits of DMD continuation (0.1–3.0 quality-adjusted life-days) were very low compared with typical patient preferences regarding treatment burden.
The benefits of DMDs may not be substantial among older adults with relapsing-onset MS. Direct clinical evidence remains limited and the decision of whether to discontinue a DMD should also take into account patient preferences. It is important to gain a better understanding of how age-related changes in the trajectory of relapsing-onset MS affect treatment effectiveness among older adults.
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The authors gratefully acknowledge the BCMS clinic neurologists who contributed to the study through patient examination and data collection (current members at the time of data extraction are listed here, by primary clinic): University of British Columbia (UBC) MS Clinic: A. Traboulsee, MD, FRCPC (UBC Hospital MS Clinic Director and Head of the UBC MS Programs); A-L. Sayao, MD, FRCPC; V. Devonshire, MD, FRCPC; S. Hashimoto, MD, FRCPC (UBC and Victoria MS Clinics); J. Hooge, MD, FRCPC (UBC and Prince George MS Clinic); L. Kastrukoff, MD, FRCPC (UBC and Prince George MS Clinic); J. Oger, MD, FRCPC. Kelowna MS Clinic: D. Adams, MD, FRCPC; D. Craig, MD, FRCPC; S. Meckling, MD, FRCPC. Prince George MS Clinic: L. Daly, MD, FRCPC. Victoria MS Clinic: O. Hrebicek, MD, FRCPC; D. Parton, MD, FRCPC; K. Atwell-Pope, MD, FRCPC. The authors also thank Tom Duggan, Feng Zhu, and the Pharmacoepidemiology in MS Research Group (https://epims.med.ubc.ca/) for research support at UBC. We are indebted to all of the people with MS who contributed the data used in this study. The views expressed in this study do not necessarily reflect the views of each individual acknowledged.
The BeAMS Study Group (the long-term Benefits and Adverse effects of beta-interferon for Multiple Sclerosis): A. Shirani, Y. Zhao, C. Evans, M.L. van der Kop, G. Gustafson, J. Petkau, J. Oger. Role: Facilitated gaining funding applications and creation of the study cohort used in the simulation-related analyses in the current manuscript. Funding: Canadian Institutes of Health Research (CIHR) [MOP-93646] and the US National MS Society [#RG 4202-A-2]; 2009-12; Principal Investigator: Helen Tremlett.
Conflict of interest
Natalie Schwehr, Karen Kuntz, Eva Enns, Nathan Shippee, Elaine Kingwell, Helen Tremlett, Adam Carpenter, and Mary Butler have no conflicts of interest that are directly relevant to the contents of this article. Eva Enns has received consulting fees from ViiV Healthcare for work unrelated to this manuscript. Helen Tremlett is the Canada Research Chair for Neuroepidemiology and Multiple Sclerosis. Current research support was received from the National Multiple Sclerosis Society, the Canadian Institutes of Health Research, the Multiple Sclerosis Society of Canada, and the Multiple Sclerosis Scientific Research Foundation. In addition, in the last 5 years, she has received research support from the Multiple Sclerosis Society of Canada (Don Paty Career Development Award); the Michael Smith Foundation for Health Research (Scholar Award), and the UK MS Trust; speaker honoraria and/or travel expenses to attend continuing medical education (CME) conferences from the Consortium of MS Centers (2013, 2018), the National MS Society (2014, 2016, 2018), European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (2013, 2014, 2015, 2016, 2017, 2018, 2019), Biogen Idec (2014), and American Academy of Neurology (2013, 2014, 2015, 2016, 2019). All speaker honoraria are either declined or donated to an MS charity or to an unrestricted grant for use by Helen Tremlett’s research group. Adam Carpenter has received research funding for participation in clinical trials involving medications (interferon-β, natalizumab) discussed in this manuscript.
Natalie Schwehr received funding that partially supported this project, i.e. a Thesis Research Travel Grant from the University of Minnesota and 3 months of support as an Advanced Research Program Scholar under the University of Minnesota’s NIH Clinical and Translational Science Award (UL1TR002494). The funding sources played no role in the design, methods, data, or interpretation of the results of the study.
Ethical approval was gained from the University of Minnesota Institutional Review Board and the UBC Clinical Research Ethics Board.
Simulation model parameters were derived from analyses of a patient cohort (access to these data are restricted to on-site in Vancouver, BC, Canada) and published literature. The resulting parameters are presented in the Methods section and in the accompanying tables.
Members of “The BeAMS Study group” are listed in the Acknowledgement section.
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Schwehr, N.A., Kuntz, K.M., Enns, E.A. et al. Informing Medication Discontinuation Decisions among Older Adults with Relapsing-Onset Multiple Sclerosis. Drugs Aging (2020) doi:10.1007/s40266-019-00741-1