Cladribine in Relapsing Multiple Sclerosis Preserves Cognition, Improves HRQoL

Treatment with cladribine tablets leads to preserved cognition and improvements in health-related quality of life (HRQoL) in patients with relapsing multiple sclerosis (MS), according to study results presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2025, held in West Palm Beach, Florida from February 27 to March 1.

The CLARIFY-MS study (ClinicalTrials.gov Identifier: NCT03369665) had previously demonstrated an improvement in HRQoL and preservation of cognition with cladribine  at 2 years in patients with relapsing MS, but long-term data are limited.

In the present study, researchers conducted a 2-year extension of CLARIFY-MS to evaluate HRQoL and cognitive function data at 4 years. The exploratory, multicenter, open-label, single-arm, phase 4 CLARIFY-MS Extension study assessed patients with highly active relapsing MS who completed the parent study. The parent study included a period of active dosing for the first 2 years, followed by a treatment-free period for the majority of participants in years 3 and 4 of the extension study.

The researchers measured HRQoL using the MS Quality of Life (MSQoL)-54 physical and mental health composite scores (PHCS, MHCS), and they used the Brief International Cognitive Assessment for MS (BICAMS) to measure cognitive function. They compared HRQoL and cognitive function scores at 4 years after the initial cladribine dose with the scores at baseline and at 24 months from the parent study.

The researchers analyzed data for treatment-naive patients (n=74), treatment-experienced patients (n=206), and all patients combined (n=280). The Pearson product-moment correlation coefficient was used to assess the correlation between MSQOL-54 scores and the BICAMS parameters, which consist of the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-II (CVLT-II), and the Brief Visuospatial Memory Test-Revised (BVMT-R).

In the total population, MSQoL-54 scores improved at 4 years after initiation of cladribine vs parent-study baseline. Statistically significant changes were observed for both the physical and mental health components (P =.003 and P <.0001, respectively).

A numerically higher improvement at 4 years vs baseline was observed for MSQoL-54 scores in the treatment-naive group (n=70) vs the treatment-experienced group (n=195) across physical and mental health components. In addition, the improvements recorded for MSQoL-54 scores at 2 years in the parent study were sustained through the 2 treatment-free years of the extension study, and SDMT, CVLT-II, and BVMT-R scores remained stable at 4 years.

At year 4, correlation was observed between the BICAMS components and the MSQoL-54 scores, suggesting a relationship between better physical and mental health and better cognitive function in cladribine-treated patients with relapsing MS.

“Treatment with [cladribine tablets] provided sustained benefits for HRQoL and cognition in patients with [relapsing MS], extending up to 4 years after the initial dose,” the researchers concluded.