Multiple Sclerosis Drugs Slow Disability Most When Started Young, MSBase Study Finds

Disease-modifying therapies for relapsing multiple sclerosis appear to curb long-term disability worsening most strongly when treatment begins in early adulthood, according to a large population-based longitudinal study drawing on the international MSBase registry. Median follow-up reached 9.4 years, with an interquartile range of 4.7 to 15.6 years, and 70.9 percent of participants were female.

The study addressed a persistent uncertainty in MS care. Disease-modifying therapies (DMTs) are well established as reducers of inflammatory activity in relapsing MS, but their long-term effects on disability worsening, and how those effects vary with the age at which treatment starts in routine clinical practice, have remained unclear.

Treatment exposure in the cohort was substantial. Overall, 87.9 percent of participants received DMTs, with 48.7 percent initiating high-efficacy therapy and 45.9 percent initiating low-efficacy therapy. Both treatment classes were associated with more favourable disability trajectories across most transitions, including an increased likelihood of improvement.

The central finding concerned age. Treatment effects were strongly age-dependent, with the greatest benefit observed in younger adults aged 18 to 30 years at treatment initiation. The benefit attenuated through midlife, spanning ages 30 to 50, and became weaker or inconclusive after age 50, particularly for transitions to secondary progressive MS. In the 5-year %IDP analyses, the inhibitory effect of treatment declined monotonically with age.

High-efficacy therapy conferred greater inhibition of disability progression than low-efficacy therapy, and notably, the evidence indicated that benefit from high-efficacy treatment persisted into older age. This distinction matters because it suggests the two broad treatment tiers do not simply mirror each other with different magnitudes; the evidence indicated that benefit from high-efficacy treatment persisted into older age, while effects after age 50 were weaker or inconclusive, particularly for transitions to secondary progressive MS.

The multistate model’s random-effects structure revealed two latent subgroups within the cohort: a rapid-worsening group comprising 76.1 percent of participants and a stable or improving group comprising 23.9 percent. These subgroups differed markedly in progression hazards and recovery potential, indicating that beneath the population-level averages lies substantial heterogeneity in how individual patients’ disability evolves over time. The authors argue this heterogeneity supports personalised treatment strategies, improved risk stratification, and enriched clinical trial design, in which patients at high risk of rapid worsening could be identified and targeted more precisely.

The study’s conclusions are framed carefully. In this large real-world cohort, DMTs were associated with sustained but age-dependent reductions in disability progression. The observational design means the findings describe associations rather than experimentally demonstrated causal effects. Because the analysis drew on routine clinical practice data from the international MSBase registry, it captures treatment effects as they occur in real-world practice.

For clinicians and researchers, the implications are twofold. First, the age gradient in treatment benefit suggests that early initiation of therapy may offer the greatest window for altering the long-term disability trajectory in relapsing MS. Second, the identification of latent progression subgroups demonstrates that statistical models capable of accounting for unobserved heterogeneity can uncover structure in patient outcomes that conventional analyses miss. The authors position these insights as directly relevant to personalised medicine in MS and to the design of future clinical trials that enrich enrolment with patients most likely to progress.

The work, conducted by Valery Fuh-Ngwa, Amin Zarghami, Julie A. Campbell, Yuan Zhou, Ingrid van der Mei, Bruce V. Taylor and colleagues across the MSBase Study Group, examined how age modifies the relationship between DMT exposure and disability progression in relapse-onset MS. By modelling transitions across clinically meaningful EDSS states, including the transition to secondary progressive MS, and by jointly estimating worsening and improvement, the study offers a granular picture of treatment effects that single-outcome analyses cannot provide. As DMT options continue to expand and questions about treatment sequencing intensify, evidence of this kind, grounded in long-term registry data from routine practice, will be central to deciding when in a patient’s life the therapies are likely to deliver the most durable protection against disability.

Subject of Research: Age-dependent effects of disease-modifying therapies on disability worsening in adult relapsing multiple sclerosis using the MSBase registry

Article Title: Disease-modifying therapies in managing disability worsening in adult relapsing multiple sclerosis: a population-based longitudinal study using the MSBase registry

Article References: Fuh-Ngwa, V., Zarghami, A., Campbell, J. A., Zhou, Y., van der Mei, I., Willekens, B., Kalincik, T., Laslett, L. L., Lechner-Scott, J., Ozakbas, S., Duquette, P., Gerlach, O., Maimone, D., Gouider, R., Butzkueven, H., Lalive, P., Patti, F., Prat, A., Girard, M., … the MSBase Study Group (2026). Disease-modifying therapies in managing disability worsening in adult relapsing multiple sclerosis: a population-based longitudinal study using the MSBase registry. BMC Medicine. https://doi.org/10.1186/s12916-026-05365-y

Image Credits: AI Generated

DOI: 10.1186/s12916-026-05365-y

Keywords: multiple sclerosis, disease-modifying therapies, disability progression, MSBase registry, EDSS, secondary progressive MS, age at treatment initiation, high-efficacy therapy, low-efficacy therapy, multistate model, real-world evidence, personalised medicine