A RECENT multicentre, randomised clinical trial has found that discontinuing first-line disease-modifying therapy (DMT) in patients with long-term stable multiple sclerosis (MS) led to inflammatory disease activity recurrence in 17.8% of cases, compared to none in the continue group.
This study explored whether first-line DMT could be safely discontinued in adults aged 18 and older with long-term stable relapsing-onset MS. Given the significant costs, treatment burden, and potential adverse effects of prolonged immunomodulatory therapy, there is a growing clinical interest in evaluating the safety of discontinuation.
The DOT-MS trial was conducted across 14 Dutch centres between July 2020 and March 2023. Participants were adults with relapse-onset MS who had been relapse-free and MRI-stable for five years while on first-line DMT. A total of 89 participants (median age: 54 years; 67.4% female) were randomised 1:1 to either continue or discontinue their DMT. After a median follow-up of 15.3 months, the trial was terminated early due to higher-than-expected inflammatory disease recurrence. In the discontinue group, 8 out of 45 participants (17.8%) experienced inflammatory disease activity—primarily radiological evidence—compared to none in the continue group (0 of 44). Two individuals in the discontinue group experienced clinical relapses. The median time to disease activity recurrence was 12 months.
The findings highlight that even in patients with long-term stable MS, discontinuation of first-line DMT can result in inflammatory disease activity recurrence in approximately 20% of cases. While the sample size was relatively small, this trial offers valuable insights into treatment decisions, especially for younger patients, as it complements previous studies, such as the DISCOMS trial, which focused on older individuals. In clinical practice, these results underscore the importance of careful patient selection and close monitoring when considering DMT discontinuation. Future research, including biomarker studies and larger cohorts, may further refine our understanding and support evidence-based decision-making in MS management.
Katrina Thornber, EMJ
Reference
Coerver EME et al. Discontinuation of first-line disease-modifying therapy in patients with stable multiple sclerosis: the DOT-MS randomized clinical trial. JAMA Neurol. 2024;DOI:10.1001/jamaneurol.2024.4164.
