Real-Life Experience of the Effects of Cladribine Tablets on Lymphocyte Subsets and Serum Neurofilament Light Chain Levels in Relapsing Multiple Sclerosis Patients

Abstract

Although cladribine induces sustained reductions in peripheral T and B lymphocytes, little is known about its effect on axonal damage reduction in multiple sclerosis (MS), which could be demonstrated by assessing the serum neurofilament light chain (sNfL) levels. We investigated the reduction/reconstitution of different lymphocyte subsets (LS) by verifying the correlation with no evidence of disease activity (NEDA) and the variation in sNfL levels during cladribine treatment. We analysed 33 highly active relapsing MS patients and followed them up for 12 ± 3.3 months; blood samples were collected at treatment start (W0) and after 8, 24 and 48 weeks. Seventeen patients (60.7%) showed NEDA during the first treatment. At week 8, we observed a significant decrease in B memory cells, B regulatory 1 CD19+/CD38+ and B regulatory 2 CD19+/CD25+, a significant increase in T regulatory CD4+/CD25+, a slight increase in T cytotoxic CD3+/CD8+ and a non-significant decrease in T helper CD3+/CD4+. Starting from week 24, the B subsets recovered; however, at week 48, CD19+/CD38+ and CD19+/CD25+ reached values near the baseline, while the Bmem were significantly lower. The T cell subsets remained unchanged except for CD4+/CD25+, which increased compared to W0. The LS changes were not predictive of NEDA achievement. The sNfL levels were significantly lower at week 24 (p = 0.046) vs. baseline. These results could demonstrate how cladribine, by inflammatory activity depletion, can also reduce axonal damage, according to the sNfL levels.

Serum Neurofilament Light Chain as Biomarker for Cladribine-Treated Multiple Sclerosis Patients in a Real-World Setting

“…SNfL reductions among our cohort were clinically accompanied by amelioration of median EDSS. Our results are in line with a recent Italian study, which observed a similar strong reduction of sNfL at 24 weeks among 18 MS patients [ 9 ]. While the exact mode of action of CLAD remains elusive, the impact on central nervous system inflammation appears mainly attributed to the peripheral consequences of the drug on circulating lymphocytes [ 10 ].…”

Cladribine tablets in Relapsing-Remitting Multiple Sclerosis preferentially target B-cells

“…Whereas the evidence on the effect of CladT on T cells is more variable with some studies noting a significant decrease in T cell number with delayed repletion 15,28 , whilst others reported a less pronounced effect on the overall T cell population with involvement of CD4+ T cells or central memory T cells 26,29,30 , or no or limited effect on CD8+ T cells 27,29 . We noted in our cohort better depletion in CD4+/CD8+ central memory, effector memory and TEMRA T cells after the second cycle of CladT 26 , but with an early compensatory rise regulatory T cells (FoxP3+) after the first course of CladT reaching a high at week 3 similar to some other findings 31 .…”