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

作者：F. Ammoscato, M. Wafa, J. Skonieczna, J. Bestwick, Rosemary Monero, Michael Andrews, S. De Trane, D. Holden, Ashok Adams, Lucia Bianchi, Ben Turner, M. Marta, K. Schmierer, David Baker, G. Giovannoni, S. Gnanapavan · 发表于：medRxiv · 年份：2024 · DOI：10.1101/2024.03.28.24304956 · 被引用次数：8 · 研究领域：Medicine

Recently it has been shown that treatments targeting B cells in multiple sclerosis (MS) are effective in controlling disease activity. B cells contribute to the pathogenesis of MS via antigen presentation, T cell activation, and antibody production. In the chronic progressive cladribine trial, some patients treated with cladribine had a significant decline in oligoclonal band number. However, the mode of action of cladribine tablets (CladT) on peripheral immune cells and its biological activity within the CNS remains to be determined further. The CladB study is a longitudinal prospective investigation of CladT treatment in relapsing-remitting MS (RRMS). Blood was sampled at Day 0, 1, 5, then once a week for 8 weeks, fortnightly up to 24 weeks, and once a month till 96 weeks for immune cells. This was compared to a historical cohort of alemtuzumab treated samples for one month. Paired cerebrospinal fluid (CSF) and blood were also taken at Day 0, 48 and 96 weeks after initiating CladT for Kappa and Lambda-free light chain ([kcy]FLC, {lambda}FLC) index, oligoclonal bands (OCBs), immunoglobulin indices, inflammatory mediators and neurofilament light chain (NfL). Participants also underwent clinical and magnetic resonance imaging brain assessments. Ten participants (3 male, 7 female, mean age 35.9 {+/-} 10.5 (SD) and Expanded disability Status Scale 2.5 (range 0-6) at baseline were enrolled. B cells, in particular memory B cells, were heavily depleted by CladT. Alemtuzumab, conver...