Siponimod for relapsing-remitting multiple sclerosis: a single-center, real-world cohort study in China.

BACKGROUND

Siponimod is a new-generation sphingosine-1-phosphate (S1P) receptor modulator that has demonstrated efficacy and tolerability in patients with secondary progressive multiple sclerosis (SPMS) in pivotal trial. However, real-world data on its use in relapsing-remitting MS (RRMS) remain limited. This study aimed to evaluate the effectiveness and safety of siponimod in RRMS patients in a real-world clinical setting.

METHODS

This was a retrospective, single-center cohort study including RRMS patients treated with siponimod between September 2020 and May 2025. Effectiveness outcomes included annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS), and no evidence of disease activity (NEDA3) status. Cognitive and motor performance were explored in a predefined subgroup using the Symbol Digit Modalities Test (SDMT), 9-Hole Peg Test (9HPT), and Timed 25-Foot Walk (T25FW).

RESULTS

Among 77 RRMS patients identified, 68 who received siponimod for more than 6 months were included in the effectiveness analysis, including 52 treatment- naïve and 16 treatment-switched patients. In treatment- naïve patients, mean ARR decreased from 1.08 ± 0.70 to 0.10 ± 0.37 after a median treatment duration of 19.6 months (P < 0.001). Among treatment-switched patients, ARR decreased from 0.70 ± 0.50 to 0.03 ± 0.12 over a median follow-up of 23.7 months (P < 0.001). Median EDSS remained stable in both groups. At the last follow-up, the proportion achieving NEDA3 was comparable between treatment-naïve and switched group (65.4% vs. 62.5%). In exploratory subgroup analysis, siponimod was associated with a modest increase in SDMT scores and a small improvement in 9HPT performance, while no significant change was observed in T25FW. Lymphopenia was the most common adverse event, observed in 94.1% (64/68) of patients with available counts, with grade 3 lymphopenia in 61.8% (42/68).

CONCLUSIONS

Siponimod was associated with reduced relapse activity and stable disability in patients with RRMS and may provide potential cognitive benefit. Given the high incidence of lymphopenia, close monitoring of peripheral lymphocyte counts is warranted.