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

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-mm(3) voxels within a mean 1.9 months of oral cladribine initiation and similar to 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.