Discontinuation of disease-modifying therapies in patients with multiple sclerosis: A retrospective case-control study.

INTRODUCTION

The long-term benefit-risk balance of disease-modifying therapies (DMTs) in multiple sclerosis (MS) becomes increasingly relevant with ageing and prolonged disease stability. Discontinuation of DMTs has been proposed for selected patients, but its impact on disability progression remains uncertain.

OBJECTIVE

To evaluate the effect of DMTs on confirmed disability progression (CDP) in patients with previously stable MS.

METHODS

We conducted a single-center retrospective case-control study including patients with relapsing-onset MS followed between 2010 and 2025. Eligible patients had been clinically and radiologically stable for at least three years while receiving a moderate-efficacy DMT (injectables, teriflunomide or fumarates). Patients who discontinued were compared with those who continued treatment. The primary outcome was CDP at two years. Inverse probability of treatment weighting (IPTW) was applied to address imbalances in baseline data.

RESULTS

118 patients were included (56 discontinuers and 62 continuers, median age 58.19 vs 51.63 respectively, p < 0.001, without differences in sex distribution or baseline EDSS). DMT discontinuation was associated with higher risk of CDP at two years (aOR=5.10; p = 0.031). No significant differences were observed in relapse rates, MRI activity, NEDA-3 status, or sNfL levels. The risk of PIRA was higher in the discontinuation group at two years (aOR = 5.96; p = 0.036). Among patients who discontinued, higher baseline EDSS was associated with subsequent CDP.

CONCLUSIONS

Discontinuation of moderate-efficacy DMTs in stable MS patients may increase the risk of disability progression despite no clear increase in inflammatory activity.