Cladribine Is Associated With Stable Cortical Gray Matter Lesion Burden in Multiple Sclerosis: A 7T MRI Study

Abstract

Background and Purpose

Cladribine, an FDA-approved disease-modifying immunotherapy for multiple sclerosis (MS), penetrates the CSF and mitigates T cells and B cells, and thus may impact the development of cortical gray matter lesions (CLs) and leptomeningeal enhancement (LME). 7T MRI is a highly sensitive tool for monitoring these outcomes in relapsing-remitting (RR) MS.

Methods

MS subjects (n = 19, age [mean ± standard deviation]: 48.8 ± 10.0 years, 63.1% RRMS, 36.9% secondary progressive MS, Expanded Disability Status Scale [EDSS] score 4.1 ± 2.0) underwent 7T MRI with 0.7-mm³ voxels within a mean 1.9 months of oral cladribine initiation and ∼1 year later in this real-world study. CLs and LME were quantified by an expert. Wilcoxon signed rank tests and paired t-tests compared baseline to follow-up data.

Results

A total of 88.2% of subjects had CLs at baseline (mean 14.1 CLs/patient, range 1–77). No subjects accrued new CLs, and CL volume remained stable (0.33 ± 0.48 mL baseline vs. 0.31 ± 0.46 mL follow-up, p = 0.22). LME was found in 88.9% of subjects at baseline. LME foci number was stable in seven (41.2%), increased in five (29.4%), and decreased in five (29.4%) subjects at follow-up, but overall LME burden was stable (3.1 ± 1.8 vs. 3.2 ± 1.6 foci per subject, p = 1.0). No EDSS or timed 25-foot walk change was noted (both p > 0.35). No subjects had clinical relapses or new T2 or gadolinium-enhancing white matter lesions during the study.

Conclusion

These observational data suggest that cladribine therapy stabilizes cortical demyelination in MS over the first year of treatment. Overall, LME burden remained stable over 1 year; however, within-subject resolution and accrual were noted.