Up to 6 years follow-up of people with MS (n=250) receiving cladribine

ABSTRACT

Introduction: Oral cladribine is a licensed disease-modifying treatment (DMT) for highly active relapsing multiple sclerosis (RMS). We report clinical and paraclinical data collected as part of ongoing follow-up of our cohort of people with MS (pwMS) treated with subcutaneous (s.c.) cladribine personalised dosing (CPD). Objectives and Aims: To report follow-up data in pwMS treated using CPD (adjusted for weight and total lymphocyte count, TLC). Methods: CPD was offered to pwMS with signs of disease activity irrespective of their disease course. Cladribine 10 mg s.c. was given on three consecutive days (four in pwMS & gt;90kg) during week 1. Based on TLC at week 4, patients were given another 0-3 doses at week 5. A second cycle of CPD was administered 11 months later. Follow-up included recording of adverse events, relapses, annual EDSS, 9-hole peg, timed 25-foot walking, and symbol digit modalities tests. MRI (gadolinium enhancing T1 and T2 lesions), cerebrospinal fluid (CSF) neurofilament light chain (NfL) measurements and full blood counts were obtained. Results: 250 pwMS (113 RMS, 137 PMS) received CPD. 211/250 completed a second cycle. Baseline age 45 (17-72) years and baseline EDSS 0-8.5. The safety and tolerability profile of CPD was generally very good. Six severely disabled pwMS died (one each from influenza, encephalitis, hypoxic brain injury due to choking, COVID19 pneumonia, haemopericardium and dissecting aortic aneurysm and unknown [prior EDSS 9.5]). One myocardial infarction, two breast cancers, one pulmonary embolism occurred, and three severe allergic skin reactions without long term sequelae. Severe lymphopenia (WHO grade 3-4) occurred in 7% despite personalised dosing. In 74/155 pwMS (47.7% of those with EDSS data available), EDSS remained stable or improved at follow up (median 2.9 years). In n=37, mean pre- and post-treatment CSF-NfL measurements at -4.4 and 11.3 months, respectively, were 1079pg/ml (CI 557, 1601) and 508pg/ml (CI 330, 686). Conclusions: Our ongoing observations of this uncontrolled real world cohort suggests CPD is a safe, well tolerated treatment for pwMS with disease activity. Efficacy of cladribine in preserving upper limb function in advanced MS (EDSS 6.5-8.5) will be tested in the ChariotMS trial.