The impact of age on efficacy and safety of disease modifying treatment—insights from the Austrian Multiple Sclerosis Treatment Registry

Introduction

Efficacy and safety considerations in the treatment of multiple sclerosis (MS) change over a person's lifetime due to immunosenescence and the increasing prevalence of comorbidities with advancing age.

Objectives/aims

To evaluate the overall efficacy and safety of disease-modifying therapies in MS patients across different age groups using prospectively collected real-world data from a nationwide observational cohort.

Methods

We included patients from the Austrian MS Treatment Registry (AMSTR) who were receiving treatment with Alemtuzumab, Cladribine, Dimethyl fumarate, Fingolimod, Natalizumab, Ocrelizumab, Ofatumumab, Ozanimod, Ponesimod, Siponimod, and Teriflunomide for at least 12 months as of March 2025. Patients were categorized into two age groups: < 50 years (n = 1,459) and ≥ 50 years (n = 658).

A generalized linear model (GLM) and Cox proportional hazards models were applied to assess treatment effects on annualized relapse rates (ARR) and changes in the Expanded Disability Status Scale (EDSS), including both progression and improvement.

Results

Over a mean treatment duration of 6.0 years (younger cohort) and 7.8 years (older cohort), the estimated mean ARR was 0.12 and 0.09, respectively (p < 0.001). Cox regression analysis of time to first relapse yielded a hazard ratio (HR) of 1.34 (95% CI 1.12–1.60, p = 0.001), indicating a significantly higher relapse risk for the younger cohort.

For sustained EDSS progression at 12 and 24 weeks, the corresponding HRs were 0.76 (95% CI 0.64–0.912, p = 0.003) and 0.70 (95% CI 0.58–0.85, p < 0.001), respectively, demonstrating a higher risk of disability progression in the older cohort.

Conclusion

Our findings indicate that approximately one-third of treated MS patients in our registry are aged 50 years or older, underscoring the substantial presence of older patients in contemporary MS treatment cohorts. Furthermore, efficacy outcomes, including ARR and EDSS progression, differed significantly between younger and older age groups. These results suggest that both disease activity and chronological age are primary determinants of treatment outcomes.