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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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Patient-reported outcomes (PRO) are increasingly utilized as part of the routine clinical assessment in people with multiple sclerosis (pwMS). The long-term effect of disease modifying therapies (DMTs) and their discontinuation on PRO measures remains largely unknown., Methods: Two pwMS groups treated with natalizumab were selected from the New York State MS Consortium (NYSMSC) database. The first group utilized long-term follow-up data of pwMS that either still continue natalizumab treatment or discontinued. Minimal requirement of three visits (before natalizumab initiation, during treatment and after discontinuation/latest follow-up) was implemented. The second group consisted of pwMS that completed PRO questionnaire on the day of the infusion and 7 days later PROs were assessed using the LIFEware System™ that assesses limitations in multiple physical and psychosocial domains. Additional physical disability was assessed using Expanded Disability Status Scale (EDSS) and Timed 25-ft walk test (T25FWT). PRO reports were Rasch-transformed, ranging from 0 to 100, with higher scores indicating a better outcome. Linear mixed-effect models and paired analyses were utilized., Results: Within the prospective cohort, 242 pwMS were followed on average of 6.5 years. Greater number of PRO domains worsened in the 141 pwMS that discontinued natalizumab when compared to 101 pwMS that remained on the drug (10 vs. 2 PRO domains). PwMS that discontinued natalizumab had significant decline in PROs regarding lower extremities, bladder and bower control and psychosocial aspects (feeling lonesome). Contrarily, pwMS that continued natalizumab had significant improvement in bladder and bowel PRO measures. Seven days after the natalizumab infusion, the 67 pwMS from the prospective cohort reported improvement in PRO measures of fatigue (62.8 vs. 66.4, p = 0.019), bladder limitations (80.3 vs. 85.0, p = 0.012), and feelings of lonesomeness (81.2 vs. 88.0, p = 0.009)., Conclusion: Continuous natalizumab treatment provides long-term stability or improvement in PRO measures. Natalizumab also provides short term improvements recorded after the infusion., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Judicious multiple sclerosis (MS) diagnosis and early start of disease modifying therapy significantly improves long-term disability outcomes in persons with MS (pwMS). Retrospective analysis based on 25-year New York State MS Consortium (NYSMSC) data determined the effect of changes in the respective diagnostic criteria in shortening the time between symptom onset to MS diagnosis. Based on 9378 current and historical MS cases, there was a significant decrease in time to diagnosis in pwMS from 1982-2001 to >2017 periods (average 4.2 vs. 1.1 years, p < 0.001). Additional improvements and better implementation of the MS diagnostic criteria can further decrease the diagnosis lag.

Background: Multiple sclerosis (MS) patients with stable disease course might view continued treatment as unnecessary. However, guidelines regarding treatment discontinuation are currently lacking., Objective: To assess the clinical course after treatment discontinuation in MS patients with long disease duration., Methods: Patients who discontinued disease-modifying treatments (DMTs) and not resume treatment (n = 216) were extracted from New York State MS Consortium (NYSMSC) and followed across three time points (average 4.6 years). Stable course was defined as no change in Expanded Disability Status Scale (EDSS) scores (<1.0 increase if EDSS<6.0 or <0.5-point increase if EDSS≥6.0) from baseline (time 1) to DMT discontinuation (time 2). Both stable and worsening MS patients were later assessed again after the DMT discontinuation (time 3). Additional analyses were performed based on disease subtype, type of medication, age cut-off of 55 and EDSS of 6.0., Results: From the cohort of 216 MS patients who discontinued DMT, 161 (72.5%) were classified as stable before DMT discontinuation. After DMT discontinuation, 53 previously stable MS patients (32.9%) experienced disability worsening/progression (DWP). 29.2 and 40% of previously stable RRMS and SPMS respectively had DWP after DMT discontinuation. Over two years after DMT discontinuation, the rate of DWP was similar between patients younger or older than 55 years (31.1% vs 25.9%, respectively). MS patients with EDSS≥6.0 had greater DWP when compared to less disabled patients while remaining on therapy as well as after discontinuation (40.7% vs 15.4%, p < 0.001 and 39.6% vs 15.2%, p < 0.001, respectively)., Conclusion: MS patients with stable disease course experience DWP after treatment discontinuation, with no clear relation to age and disease subtype. Patients with EDSS≥6.0 are at higher risk for DWP., (Copyright © 2021 Elsevier B.V. All rights reserved.)