Background: Relapsing-onset multiple sclerosis (MS) typically starts in early- to mid-adulthood, yet the trajectory of disease activity over the subsequent lifetime remains poorly defined. Previous studies have not quantified the age-specific portion of decreases in annualized relapse rates (ARR). Objective: The aim of this article is to determine, under a range of disease-related assumptions, the age-specific component of decreases in ARR over time among adults with relapsing-onset MS. Methods: We used a simulation modeling approach to examine a range of assumptions about changes in ARR due to age versus disability status. Scenarios included variations in initial ARR and rate of worsening on the Expanded Disability Status Scale. Model parameters were developed through analysis of MS patients in British Columbia, Canada, and literature review. Results: We found a substantial age-specific decrease in ARR in all simulated scenarios, independent of disability worsening. Under a range of clinically plausible assumptions, 88%–97% of the decrease was attributed to age and 3%–13% to disability. The age-specific decrease ranged from 22% to 37% per 5 years for a wide range of initial ARR (0.33–1.0). Conclusion: Decreases in ARR were due mostly to age rather than disability status. To facilitate informed decision making in MS, it is important to quantify the dynamic relationship between relapses and age.
Bibliographical noteFunding Information:
The BeAMS Study group: Long-term Benefits and Adverse Effects of Beta-interferon for Multiple Sclerosis: Shirani A.; Zhao Y.; Evans C.; van der Kop M.L.; Gustafson G; Petkau J; Oger J. Role: facilitated gaining funding 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; PI: Tremlett). We gratefully acknowledge contributions to this research project including but not limited to the following individuals: BCMS clinic neurologists who contributed to the study through patient examination and data collection (current members at the time of data extraction listed here by primary clinic): 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. UBC research support: Tom Duggan, Feng Zhu, and the Pharmacoepidemiology in MS Research Group (https://epims.med.ubc.ca/). We are indebted to all of the people with MS who contributed to the data used in this study. The views expressed in this study do not necessarily reflect the views of each individual acknowledged. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded in part by a Thesis Research Travel Grant from the University of Minnesota and the University of Minnesota?s NIH Clinical and Translational Science Award: UL1TR002494 (Advanced Research Program Scholar). The funding sources played no role in the design, methods, data, or interpretation of the results of the study. Helen Tremlett is the Canada Research Chair for Neuroepidemiology and Multiple Sclerosis. Current research support 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; and speaker honoraria and/or travel expenses to attend CME conferences from the Consortium of MS Centers (2013, 2018), the National MS Society (2014, 2016, 2018), ECTRIMS (2013, 2014, 2015, 2016, 2017, 2018, 2019), Biogen Idec (2014), 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 her research group.
© The Author(s), 2019.
- Multiple sclerosis
- decision support techniques