Positive impact of cladribine tablets on reducing brain atrophy in patients with relapsing-remitting multiple sclerosis: A longitudinal study

Background: Measuring brain volume changes over time is an objective and dependable surrogate marker for the pathological processes that damage the brain in relapsing-remitting multiple sclerosis (RRMS). These measures are particularly valuable for monitoring the long-term impact of immunomodulatory treatments such as cladribine. Objectives: To evaluate the long-term impact of oral cladribine treatment on brain volume loss in patients with RRMS. Methods: This real-world study processed magnetic resonance imaging (MRI) scans using FreeSurfer’s recon-all-clinical pipeline leveraging SynthSeg for brain segmentation. Piecewise linear regression was used to analyze brain atrophy changes over 4.5 years before and after cladribine treatment and estimate the time breakpoint of atrophy rate change. Results: A total of 448 MRI exams from 102 RRMS patients were analyzed. Before the initiation of cladribine treatment, brain atrophy rates were significantly steep with an α1 slope between −1.27 and −0.62 for the Thalamus, DGM, Subcortical GM, Cerebral WM, and BP. Over 2 years after treatment, breakpoints marked a shift in atrophy rates, with post-breakpoint slopes (α2) becoming non-significant, reflecting stabilization of brain atrophy. Conclusions: Cladribine treatment in highly active RRMS patients protects the brain from atrophy, with stabilization occurring over 2 years after initiation. The extended observation period highlights its sustained benefits compared with shorter clinical trials.