Impact of multiple sclerosis disease-modifying therapies on chronic lesion tissue expansion

Background: Chronic lesion tissue expansion (CLTE) reflects slow, concentric growth of established multiple sclerosis (MS) lesions and is linked to central brain atrophy and disability progression. Whether existing MS disease-modifying therapies (DMTs) differentially influence this aspect of progressive MS biology remains unclear. Objectives: To compare the effect of current DMTs on CLTE in a multicentre, real-world MS cohort. Methods: We conducted a retrospective, observational study using linked clinical data from MSBase and the MSBase Imaging Repository. Data from patients aged ⩾18 years with ⩾3 longitudinal MRI scans, and 7 therapies with ⩾100 stable treatment epochs were included. Therapy effects on CLTE, new T2 lesions, and brain atrophy were assessed using epoch-based covariate-adjusted generalised estimating equation models, with fingolimod as a comparator. Result: The cohort included 564 patients contributing 1648 stable treatment epochs. After adjustment for demographic, clinical, and imaging covariates, B-cell depleting therapy was the only DMT associated with significantly lower CLTE (β = −4.03, p = 0.017) relative to fingolimod. CLTE was independently associated with age, baseline lesion volume, and centre effects. Conclusions: B-cell depletion is associated with reduced CLTE, a promising biomarker of progressive MS biology.