Real-world experience of cladribine treatment in relapsing-remitting multiple sclerosis: A Danish nationwide study.

Abstract

Cladribine is a nucleoside analogue interfering with synthesis and repair of DNA. Treatment with cladribine leads to a preferential reduction in lymphocytes, resulting in profound depletion of B-cells with a rapid recovery of naïve B-cells, while T-cell show a lesser but long-lasting depletion It is approved for treatment of relapsing multiple sclerosis (MS). Cladribine tablets 3.5mg/kg bodyweight are administered in two yearly treatment courses, each including two treatment series lasting 4 or 5 days, one at the start of the first month and the other at the start of the second month. To describe treatment patterns of cladribine in a real-world setting. Registry based observational cohort study with prospectively enrolled cases from December 2017 through June 2021. The data source is The Danish Multiple Sclerosis Registry, which is a near complete nationwide population-based registry. Outcomes were length of the treatment, preceding and following treatments, treatment response, and safety data. In total 268 patients had started therapy with cladribine tablets, 89 men and 179 women, with a median age of 40 years (interquartile range (IQR) 32-48. The disease course was relapsing-remitting MS in 97.8% of the patients, and at treatment start the median time from disease onset was 8.1 years (IQR 4.2-14.5) and EDSS 2.5 (IQR 1.5-3.5). Thirty-four patients (12.7%) were treatment naïve while 56 (20.9%) had received one previous disease-modifying therapy (DMT), 67 (25.0%) two, and 111 (41.4%) three or more previous DMTs. In total, 214 (80.0%) patients had completed the full treatment of two courses of cladribine, while 54 (20.0%) had received only one course of cladribine tablets. The median follow-up time after cladribine initiation was 34.7 months (IQR 23.3-43.7). Compared with an annualized relapse rate (ARR) of 0.67 (95% CI [0.56, 0.79]) in the year prior to start of cladribine, ARR was reduced to 0.11 (95% CI [0.08, 0.15]) in year 0-2 after 3-month re-baseline with cladribine (84.8% reduction). Adverse events, reported in 44 (16.4%) of the patients, were mild or moderate, and herpes zoster was only reported in 2 patients. In total, 30 (11.2%) patients discontinued cladribine treatment, of whom 7 (2.6%) discontinued because of adverse effects and 12 (4.5%) discontinued because of disease activity. In this nationwide review of all Danish patients starting therapy with cladribine tablets in a real-world setting, cladribine treatment was safe, and the therapeutic response was as expected from previous clinical trials. A prolonged observation period is necessary to assess the long-term benefit and risk of cladribine.