Disease-modifying treatment, long-term outcomes and transition to progressive multiple sclerosis: data based on the New York State MS Consortium

Background: The impact of disease-modifying treatments (DMTs) on multiple sclerosis (MS) long-term outcomes is continuously evolving. Retrospective analyses of large and long-term registries could provide information regarding general disease trajectories and risk factors that are commonly not investigated in shorter clinical trial settings. Methods: Retrospective observational study of people with MS (pwMS) registered in New York State MS Consortium (NYSMSC) since 1996. Disability outcomes of reaching sustained Expanded Disability Status Scale (EDSS) scores of 4.0, 6.0 and transition to secondary-progressive MS (SPMS) were confirmed at follow-up. Four DMT categories were determined (1) continuous DMT use, (2) discontinued DMT, (3) (re)started DMT and (4) never treated with DMT. Patient-reported outcomes (PRO) were acquired using LIFEware system. Kaplan–Meier survival curves and adjusted analysis of covariance (ANCOVA) were used to determine the rate and factors related to disability progression. Results: Total of 1893 pwMS were included with baseline average age of 43.2 years (SD = 10.4), 9.6 years of disease duration (SD = 8.8), median EDSS of 3.0 (IQR 2.0–3.5) and average follow-up time of 6.9 years (SD = 4.9). In addition to being male, older, more disabled and reporting worse PROs at baseline, pwMS who discontinued DMT had more than 5.5 times greater risk of reaching sustained EDSS of 4.0 (OR = 5.56, 95% CI 2.78–11.0, p < 0.001). Similarly, pwMS who discontinued DMT during the NYSMSC follow-up had 3.8- and 4.7-times greater risk to reach sustained EDSS 6.0 (OR = 3.86, 95% CI 2.12–7.02, p < 0.001), and to transition to SPMS (OR = 4.77, 95% CI 2.9–7.87, p < 0.001). Propensity matching analysis confirmed the worse clinical outcomes. Conclusions: In addition to known predictors of long-term clinical outcomes, pwMS who discontinue DMT have worse long-term disability trajectory when compared to both early and late DMT starters. PRO-based indicators may suggest worse clinical outcomes.