Cladribine slowing brain loss

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If you can remember back a few years ago and ProfG back-tracked from enthusiasm for cladribine and ocrelizumab to suggest that they were not as good as alemtuzumab at affecting atrophy of the brain, suggesting that T cells are important.

This new study was done over a decade ago, in the CLARITY trial.

Now I have no problems with the view of ProfG, but I did think that comparing results from trials done two years from diagnosis (CARE-MS-1) with people treated 9 years after diagnosis was not a failr comparison.

Indeed stashed away in the murky depths of the supplementary data from the ORACLE cladribine trial in optic neuritis and early diagnosis. It was seen that the rate of atrophy was the same as aging.

This needs to be replicated

Cortese R, Battaglini M, Sormani MP, Luchetti L, Gentile G, Inderyas M, Alexandri N, De Stefano N. Reduction in Grey Matter Atrophy in Patients with Relapsing Multiple Sclerosis Following Treatment with Cladribine Tablets. Eur J Neurol. 2022 Sep 27. doi: 10.1111/ene.15579d of print.PMID: 36168741

Background: Measures of atrophy in the whole brain can reliably assess treatment effect in clinical trials of patients with multiple sclerosis (MS). Trials assessing the effect of treatment on grey matter (GM) and white matter (WM) atrophy are very informative, but hindered by technical limitations. This study used a robust longitudinal method to measure GM and WM volume changes in patients with relapsing MS randomized to cladribine tablets 3.5 mg/kg (CladT3.5) or placebo in the CLARITY study.

Methods: We analyzed T1-weighted magnetic resonance sequences using SIENA-XL, from 0-6 months (CladT3.5, n=267; placebo, n=265) and 6-24 months (CladT3.5, n=184; placebo, n=186). Mean percentage GM and WM volume changes (PGMVC and PWMVC) were compared using a mixed effect model.

Results: More GM and WM volume loss was found in patients taking CladT3.5 vs those taking placebo in the first 6 months of treatment [PGMVC: CT3.5: -0.53 vs placebo: -0.25 (p=0.045); PWMVC: CladT3.5: -0.49 vs placebo: -0.34 (p=0.137)], likely due to pseudoatrophy (Getting rid of inflammation removes the swelling so the brain appears to shrink). However, in months 6 to 24, GM volume loss was significantly lower in patients on CladT3.5 than in those on placebo [PGMVC: CladT3.5: -0.90 vs placebo: -1.27 (p=0.026)]. In this period, volume changes in WM were similar in the two patient arms (p=0.52).

Conclusions: After a short period of pseudoatrophy, treatment with CladT3.5 significantly reduced GM atrophy in comparison with placebo. This adds to the relevance of GM damage in MS and may have important implications for physical and cognitive disability progression.

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