To Örebro University

Introduction: Cladribine is a deoxyadenosine analogue prodrug that induces immune reconstitution by selectively targeting B- and T-lymphocytes. Cladribine tablets (CladT) are administered in two courses, 12 months apart, for patients with relapsing multiple sclerosis (RMS). Post-marketing surveillance is important for evaluation of long-term safety and effectiveness in a real-world setting. CLADCOMS (CLADribine tablets long-term Control Of MS) is a post-marketing investigator driven study. Here we report two year prospectively obtained data for all patients included in the study.

Objectives/Aims: To investigate the proportion of patients, free of disease activity with a Cladribine treatment duration of at least 24 months.

Methods: CLADCOMS includes patients with RMS from eight academic neurology clinics in Sweden who started Cladribine treatment after 23rd of March 2018. Data is prospectively registered in the Swedish Neuroregistry using highly structured yearly follow-up. Descriptive data on relapses, MRI activity, and Patient Reported Outcome Measures were obtained from the registry.

Results: By December 2023, a total of 251 patients had been included in the CLADCOMS study. Over 58% (147 patients) of the included patients had a treatment duration with CladT for 24 months or longer. In previously treatment-naïve patients, 76.5% were relapse-free during the first 24 months of CladT treatment, and in previously natalalizumab-, dimethyl fumarate- and rituximab treated patients, relapse-free rates were 83%, 89% and 86.3%, respectively.Analysis of total B-cell lymphocyte count over time showed a significant (p<0.05) drop from baseline (0.29x109/L ±0.28) to year one (0.16x109/L ±0.13) and year two (0.14x109/L ±0.09). The proportion of CD19+/CD27+ memory B-cells dropped from 11.5% ±9.15% at baseline to 2.7% ±2.5% after the first year and to 2.4% ±2.0% after the second year of treatment. The proportions of CD19+ naïve B-cells raised over time from 61.8% ±17.8% at baseline to 79.2% ±16.2 after first year and 81.2% ±11.4 after second year of treatment.

Conclusion: CladT treatment showed clinical stability during the first two years regardless of previous treatment. The unique immune modulation helps to explain the durability of the effect of Cladribine. However, continued follow-up is needed to assess the effectiveness and safety of treatment with Cladribine to investigate time to disease re-activation after full treatment.