Treatment effects of cladribine tablets on data-driven patterns of regional grey matter atrophy in multiple sclerosis

Background: Treatment with cladribine tablets (CladT) in relapsing–remitting multiple sclerosis (RRMS) reduced global grey matter (GM) atrophy, but the effects on regional GM are unknown. Objectives: This study aimed to investigate the effect of CladT compared with placebo on magnetic resonance imaging (MRI)-derived patterns of GM atrophy. Methods: We used MRI and clinical data from the CLARITY study, including 393 people with RRMS (CladT (3.5 mg/kg), n = 200 or placebo, n = 193) at baseline, 24, 48 and 96 weeks after treatment initiation. SynthSeg-derived volume changes and GM atrophy patterns derived from source-based morphometry were analysed for group differences over time and associations with disability using mixed-effect models. Results: Deep GM (β = −0.03, p < 0.01), thalamus (β = −0.04, p < 0.01) and the brainstem–thalamus pattern (β = −0.03, p < 0.05) showed higher reduction in the placebo compared with treated group. These regions showed no effect during a predefined pseudo-atrophy period, where global volume loss was worse in the treatment group. Between W24 and W96, Expanded Disability Status Scale (EDSS) scores were associated with lower deep GM volume (β = −0.16, p = 0.001), thalamic volume (β = −0.16, p < 0.001), and the brainstem–thalamus pattern (β = −0.12, p < 0.05). Conclusion: CladT are associated with clinically relevant and slower neurodegeneration in RRMS. Strongest effects were seen in deep GM, thalamus, and brainstem, underlining the importance of regional MRI measures for assessing treatment effects.