ABSTRACT
Introduction: Cladribine is a CNS penetrant disease-modifying treatment, which - in an oral preparation (Mavenclad) - was licensed for people with highly active relapsing MS in August 2017. Our experience with cladribine dates back to 2014 when we started using subcutaneously injected cladribine as a compassionate immunotherapy in people with MS (pwMS) off-label. This programme enabled us to embed CLADRIPLAS, a mechanistic study of the effect on intrathecal B cell and plasma cell function and axonal damage focussing on progressive MS (PMS) (IRAS # 240360). Objective(s): To study the effect of cladribine on peripheral and intrathecal B and plasma cells. Aim(s): To study the effect of cladribine on oligo-clonal bands (OCB) and the level of neurofilament light (NfL) chain. Method(s): Observational study involving two lumbar punctures and phlebotomies, 6-12 months apart, to collect B cell subsets, and intrathecal plasma cell as well as neurofilament light chain (NfL) level in pwMS eligible and not eligible for cladribine treatment based on cerebro-spinal fluid (CSF) NfL, clinical and/or MRI evidence of inflammatory disease activity. Here, we report baseline cohort characteristics. Result(s): Thirty-eight pwMS were recruited (19 women, 19 men) and had their first sample collections. Eight pwMS were eligible for cladribine treatment (7 based on elevated NfL, 1 due to MRI activity). Follow-up samples have been collected in 21. Mean age at baseline was 55 years (40-76). Fourteen had primary, 24 secondary PMS. Median EDSS=6.5 (3.5-8). Twenty-one pwMS had been treated with DMT before consideration of cladribine, 17 were immunotherapy-naive. Mean CSF-NfL level was 552 (176- 2072) pg/ml. Conclusion(s): Despite restrictions due to COVID-19, 38 of 40 planned pwMS were enrolled. 7/8 were eligible based on CSFNfL level indicating the importance of using biomarkers other than MRI to establish disease activity in PMS. We expect our cohort to enable meaningful comparison between groups. CLADRIPLAS will finish in early 2023.