Discontinuation of disease-modifying therapy in stable multiple sclerosis: A systematic review and meta-analysis

Disease-modifying therapies (DMTs) are used to manage multiple sclerosis (MS), particularly in individuals with relapse-onset MS, to slow disease progression, reduce inflammation and demyelination and improve quality of life. Discontinuing treatment may pose a greater relapse risk for younger individuals with active disease, whereas the safety of treatment cessation in older, stable patients remains uncertain.

We conducted a systematic review and meta-analysis of studies comparing discontinuation of disease-modifying therapy in stable multiple sclerosis patients. Data were collected from PubMed, Embase, and Cochrane Central databases. Statistical analysis was performed using Review Manager v5.4. A random-effects model was applied to pool risk ratios (RRs) and 95 % confidence intervals, with statistical significance set at p < 0.05.

A total of eight studies, including 4517 patients (3355 in the continuation group and 1162 in the discontinuation group), were analyzed. The mean age of participants was 53 years, with 72.7 % being female. Discontinuation of disease-modifying therapy (DMT) in patients with stable multiple sclerosis (MS) was associated with a significantly higher risk of mild adverse events (RR 1.29; 95 % CI 1.15-1.46; p < 0.0001). However, the risk of relapse (RR 0.31; 95 % CI 0.03-3.21; p = 0.33), as well as moderate (RR 1.11; 95 % CI 0.97-1.28; p = 0.14) and severe adverse events (RR 0.90; 95 % CI 0.45-1.78; p = 0.75), was comparable between the two groups. Similarly, the risk of common or treatment-related adverse events, including COVID-19 (RR 0.65; 95 % CI 0.28-1.52; p = 0.32), influenza (RR 0.39; 95 % CI 0.14-1.08; p = 0.07), and abnormal white blood cell count (RR 1.03; 95 % CI 0.11-3.21; p = 9.77), did not differ significantly between the continuation and discontinuation groups.

This meta-analysis found no significant increase in relapse risk after DMT discontinuation in stable MS patients. However, outcomes varied based on patient age, prior DMT, and duration of disease stability. Agents like S1P inhibitors and natalizumab may carry higher relapse risk after cessation. Additionally, new MRI lesions were noted in some studies, highlighting the need for continued monitoring. Treatment decisions should be individualized until further long-term data become available.