Clinical Efficacy and Brain Volumetric Changes in Pediatric-Onset Multiple Sclerosis Under Teriflunomide Treatment

Background Brain volumetric imaging provides important insights into neuroaxonal injury in pediatric-onset multiple sclerosis (POMS), beyond conventional clinical measures of disease activity. Objective To evaluate the longitudinal brain volume changes in POMS patients treated with teriflunomide from disease onset, and to explore their associations with clinical outcomes, including annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) scores. Methods This retrospective longitudinal study included treatment-naïve POMS patients with standardized 1.5-tesla (T) brain MRIs at baseline and 24-month follow-up. Brain volumes were quantified using fully automated volBrain software. Clinical measures included ARR and EDSS scores. Results Sixteen patients (median age: 15 years; 62.5% female) were included. All patients received teriflunomide as a first-line therapy. Over the 24-month follow-up, the mean ARR decreased from 2.1 to 0.53 and the median EDSS remained stable. Significant reductions were observed in total brain volume ( P = .02), as well as in regional structures including the thalamus ( P = .02), total gray matter ( P = .01), amygdala ( P = .02), and limbic cortex ( P = .004). Conclusions In this real-world cohort of POMS patients treated with teriflunomide, measurable brain volume loss was observed over a 24-month period despite a reduction in relapse activity and stable EDSS scores. These findings provide exploratory evidence of longitudinal volumetric change in a teriflunomide-treated POMS cohort despite residual clinical disease activity. Given the limitations of the study design, including the absence of a control group, these results should be interpreted cautiously and warrant confirmation in larger, controlled longitudinal studies.