Summary of Research: Blood Biomarker Dynamics in People with Relapsing Multiple Sclerosis Treated with Cladribine Tablets: Results of the 2-Year MAGNIFY-MS Study

Cladribine tablets (CladT) for relapsing multiple sclerosis help reset the immune system with short treatment courses over 2 years. This analysis of MAGNIFY-MS contrasted clinical outcomes with changes in immune cells, proteins and genes over 2 years in 270 participants. Most immune cells decreased 3 months after starting CladT. Gradual recovery was seen in naïve, regulatory, and transitional B cells starting at month (M)3 and M6. Gene activity related to immune response changes was also reported. Fewer cells producing pro-inflammatory signals and more cells producing anti-inflammatory signals were detected by M24. Immunoglobulin levels mostly remained normal, and a marker of neuroaxonal damage (serum neurofilament light chain) was decreased. Significant reductions in lesion count occurred from M2 onwards. Annualised relapse rate was 0.11 (95% confidence interval: 0.09, 0.15). Over 90% of participants were free of 6-month confirmed disability progression, around 87% had no confirmed progression on 9-hole peg test and timed 25-foot walk. No significant correlations were seen between clinical parameters and lymphocyte dynamics. The safety profile was consistent with previous studies. These findings provide evidence of CladT rebalancing the immune system towards a more homeostatic and less pathogenic state.