To report safety and efficacy of subcutaneous (s.c.) cladribine as an immunotherapy for people with multiple sclerosis (pwMS).

Oral cladribine is a licensed disease-modifying treatment (DMT) for relapsing multiple sclerosis (RMS). We have experience treating a large cohort with this compound, ranging from early to advanced MS, using subcutaneous cladribine personalised dosing (CPD) since 2014.

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 >90kg) during week 1. Based on total lymphocyte count 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.

250 pwMS (113 RMS, 137 PMS) received CPD. 211/250 completed a second cycle. Baseline age 45 (17-72) years, EDSS 0-8.5. CPD was generally well tolerated. One myocardial infarction, one breast cancer, one pulmonary embolism occurred, and three severe allergic skin reactions without long term sequelae. Two severely disabled pwMS died (one influenza, one encephalitis). Lymphopenia ? grade 3 occurred in 7%. In 99/121 (82%) pwMS with baseline and 2-year follow-up data, EDSS remained stable or improved. Of 23 pwMS with elevated baseline CSF-NfL, 22 had normal levels at follow-up.

CPD was well tolerated. Efficacy in pwRMS was in line with oral cladribine trial data. Our uncontrolled real-world data suggests CPD may be an effective alternative for patients with active MS irrespective of disability level. ChariotMS (a UK multi-centre trial of oral cladribine) will establish whether there is efficacy in advanced MS (EDSS 6.5-8.5).