Cladribine tablets in relapsing-remitting multiple sclerosis preferentially target B-cells

Area of Science:

• Neuroimmunology
• Pharmacology

Background:

• B cells play a critical role in multiple sclerosis (MS) pathogenesis.
• B cell-targeting therapies have shown efficacy in managing MS activity.

Purpose of the Study:

• To quantify temporal changes in peripheral immune cells and their activity during 96 weeks of Cladribine tablets (CladT) treatment in relapsing-remitting MS (RRMS).
• To compare the immune cell profile changes with a historical alemtuzumab-treated cohort.

Main Methods:

• Ten RRMS participants received CladT, with blood samples collected at multiple intervals up to 96 weeks.
• Immune cell analysis, cerebrospinal fluid (CSF) analysis, clinical, and brain imaging assessments were performed.
• Comparison with a historical cohort treated with alemtuzumab.

Main Results:

• CladT primarily depleted memory B cells and antibody-secreting cell precursors.
• Significant reductions were observed in the kappa free light chain (κFLC) index, IgG index, and CSF CXCL-13 levels.
• CSF NfL levels were also reduced at 48 weeks, indicating a decrease in neuroinflammation.

Conclusions:

• CladT treatment leads to sustained effects on intrathecal antibody production and total IgG in RRMS patients.
• The observed reductions in CSF CXCL-13 and NfL suggest a significant impact on central nervous system inflammation.
• CladT demonstrates a favorable immunomodulatory profile in managing RRMS activity.