Jonathan Zurawski1, Bonnie I Glanz2, Alicia Chua3, Hrishikesh Lokhande3, Dalia Rotstein4, Howard Weiner2, David Engler5, Tanuja Chitnis2, Brian C Healy6. 1. Department of Neurology, Harvard Medical School, Boston, MA, USA; Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: jzurawski@bwh.harvard.edu. 2. Department of Neurology, Harvard Medical School, Boston, MA, USA; Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Boston, MA, USA. 3. Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Boston, MA, USA. 4. Department of Neurology, St. Michael's Hospital, Toronto, ON, Canada. 5. Department of Statistics, Brigham Young University, Provo, UT, USA. 6. Department of Neurology, Harvard Medical School, Boston, MA, USA; Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Boston, MA, USA; Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA. Electronic address: bchealy@partners.org.
Abstract
BACKGROUND: Although the expanded disability status scale (EDSS) is the most commonly used measure of disability for multiple sclerosis, measurement of disability accumulation is complex due to the unequal steps of the scale. OBJECTIVE: To estimate the time between EDSS scores in a large MS cohort from a single center and determine the impact of functional system scores on EDSS transitions. METHODS: 31,394 clinical visits with EDSS scores from 2054 subjects in the CLIMB longitudinal cohort study were included in our analysis. The time to each EDSS score and the time between each EDSS score were calculated using the nonparametric maximum likelihood estimate for interval censored data. For each initial EDSS value, the association between functional status scores and subsequent EDSS value was assessed using a mixed effects linear regression model, and the association with time to EDSS increase was assessed using a Cox proportional hazards model. RESULTS: The median time until EDSS 2, 3, 4, 5 and 6 in all subjects were 4.8, 15.1, 28.2, 31.2, and 32.4 years, respectively. The time intervals showed that the disability accumulation intervals from EDSS 4 to 6 were much shorter than the accumulation intervals from EDSS 0 to 3 or from EDSS 6 to 8. For EDSS of 1 or 1.5, pyramidal, cerebellar, sensory, bowel-bladder and mental system scores were associated with higher subsequent EDSS values. For higher EDSS values, only pyramidal and bowel-bladder scores maintained the association. CONCLUSIONS: Time between specific EDSS levels varies considerably. Certain functional system scores have greater predictive power for future EDSS-related disability despite same present EDSS level. These findings will assist in adaptation of the EDSS as an outcome measure to assess MS-related disability in clinical trials.
BACKGROUND: Although the expanded disability status scale (EDSS) is the most commonly used measure of disability for multiple sclerosis, measurement of disability accumulation is complex due to the unequal steps of the scale. OBJECTIVE: To estimate the time between EDSS scores in a large MS cohort from a single center and determine the impact of functional system scores on EDSS transitions. METHODS: 31,394 clinical visits with EDSS scores from 2054 subjects in the CLIMB longitudinal cohort study were included in our analysis. The time to each EDSS score and the time between each EDSS score were calculated using the nonparametric maximum likelihood estimate for interval censored data. For each initial EDSS value, the association between functional status scores and subsequent EDSS value was assessed using a mixed effects linear regression model, and the association with time to EDSS increase was assessed using a Cox proportional hazards model. RESULTS: The median time until EDSS 2, 3, 4, 5 and 6 in all subjects were 4.8, 15.1, 28.2, 31.2, and 32.4 years, respectively. The time intervals showed that the disability accumulation intervals from EDSS 4 to 6 were much shorter than the accumulation intervals from EDSS 0 to 3 or from EDSS 6 to 8. For EDSS of 1 or 1.5, pyramidal, cerebellar, sensory, bowel-bladder and mental system scores were associated with higher subsequent EDSS values. For higher EDSS values, only pyramidal and bowel-bladder scores maintained the association. CONCLUSIONS: Time between specific EDSS levels varies considerably. Certain functional system scores have greater predictive power for future EDSS-related disability despite same present EDSS level. These findings will assist in adaptation of the EDSS as an outcome measure to assess MS-related disability in clinical trials.
Authors: Leif Er Simmatis; Albert Y Jin; Sean W Taylor; Etienne J Bisson; Stephen H Scott; Moogeh Baharnoori Journal: Mult Scler J Exp Transl Clin Date: 2020-10-15
Authors: Brian C Healy; Bonnie I Glanz; Elyse Swallow; James Signorovitch; Kaitlin Hagan; Diego Silva; Corey Pelletier; Tanuja Chitnis; Howard Weiner Journal: Mult Scler J Exp Transl Clin Date: 2021-04-11
Authors: Seth N Levin; Shruthi Venkatesh; Katie E Nelson; Yi Li; Ines Aguerre; Wen Zhu; Karman Masown; Kathryn T Rimmer; Claudiu I Diaconu; Kaho B Onomichi; Victoria M Leavitt; Libby L Levine; Rebecca Strauss-Farber; Wendy S Vargas; Brenda Banwell; Amit Bar-Or; Joseph R Berger; Andrew D Goodman; Erin E Longbrake; Jiwon Oh; Bianca Weinstock-Guttman; Kiran T Thakur; Keith R Edwards; Claire S Riley; Zongqi Xia; Philip L De Jager Journal: Ann Clin Transl Neurol Date: 2021-02-22 Impact factor: 5.430