Danish registry study links cladribine to lower short-term MS relapse rates

A Danish nationwide real-world study found that people with relapsing–remitting multiple sclerosis who received cladribine had lower annualised relapse rates during the first three years of treatment than in the year before treatment, while some longer-term patterns remained difficult to predict. Annualised relapse rates declined from approximately 0.55 before baseline to about 0.23–0.25 from the start of treatment through year three. The reduction in relapse frequency was accompanied by relatively few confirmed disability-worsening events, but the combined state of no evidence of disease activity was progressively lost during longer follow-up.

The observational analysis screened the Danish Multiple Sclerosis Registry for patients with relapsing–remitting multiple sclerosis who had received at least two five-day cladribine treatment cycles and were followed for more than 90 days. From 90 days after the first dose, designated the index point, researchers analysed annualised relapse rates through year three alongside activity measures based on relapses or magnetic resonance imaging activity. They also examined time to the first 24-week confirmed disability worsening, disability progression independent of relapses, and loss of “no evidence of disease activity,” abbreviated NEDA-3.

Predictor analyses considered age, split at 45 years, disease activity before baseline, and short-term NEDA-3 status. Younger age and greater pre-baseline activity were associated with more frequent short-term disease activity. Pre-baseline activity also predicted short-term loss of NEDA-3. These findings were consistent in a validation subgroup that had completed at least four five-day cladribine cycles before year three and contributed more than three years of follow-up, a group referred to as the three-year follow-up subgroup. The subgroup analysis was assessed with Kaplan–Meier and log-rank methods.

Confirmed disability worsening and disability progression independent of relapses were uncommon. Approximately 10% of patients experienced these outcomes during the short-term period, while about 20% experienced them during longer-term follow-up. The relatively low proportions were observed even among patients aged 45 years or older. By contrast, loss of NEDA-3 resumed steadily during long-term follow-up and was largely unpredictable. Overall, the observed response appeared more favourable among older patients and among those without disease activity before baseline, although the study does not establish that cladribine caused these differences.

The findings point to strong short-term efficacy in the registry cohort, with substantially fewer annualised relapses after treatment began and comparatively rare confirmed disability-worsening events over both follow-up periods. However, the return of ongoing NEDA-3 loss means that the three-year results do not amount to uninterrupted control of all measured disease activity. Because this was an observational registry study, it cannot separate the effects of cladribine from other factors associated with relapse and disability outcomes. The small number of confirmed disability-worsening and relapse-independent progression events also limits conclusions about disability prevention. The researchers stated that optimal long-term management after cladribine treatment, and the drug’s role in preventing disability, require further research.

Subject of Research: Real-world short-term and long-term treatment outcomes with cladribine in relapsing–remitting multiple sclerosis

Article Title: Prediction of short-term and long-term responses to cladribine in relapsing–remitting multiple sclerosis: a Danish nationwide real-world study

Article References: Bramow, S., Pontieri, L., Heick, A., Thormann, A., Sejbæk, T., Rasmussen, P. V., Weglewski, A., Qadir, S. H., Christensen, J. R., Mærsk-Møller, C., Zachariassen, K., Schäfer, J., Stilund, M., Jensen, H. B., Kristensen, C. C. H., Kant, M., Sellebjerg, F., Sørensen, P. S., Magyari, M., … Danish Multiple Sclerosis Group (2026). Prediction of short-term and long-term responses to cladribine in relapsing–remitting multiple sclerosis: a Danish nationwide real-world study. Journal of Neurology, 273(11), 676. https://doi.org/10.1007/s00415-026-14152-x

Image Credits: AI Generated

DOI: 10.1007/s00415-026-14152-x

Keywords: cladribine, multiple sclerosis, relapsing–remitting MS, relapse rates, disability progression, disease activity, NEDA-3, Danish registry, real-world study, treatment response, Prediction, short-term