MS Treatment Cladribine Provides Quality of Life Benefits and Improved Cognition Over 4-Year Period

Andrzej Smyk, MD

New data from the phase 4 CLARIFY-MS extension trial (NCT04776213) continued to highlight the treatment benefits of cladribine tablets (Mavenclad; EMD Serono) on health-related quality of life (HRQoL) and cognition in patients with relapsing multiple sclerosis (RMS) for up to 4 years after the initial dose.

In the analysis, investigators compared changes in HRQoL and cognitive function among patients treated in the extension study for 4 years vs baseline and month 24 from the original CLARIFY-MS parent study. Led by Andrzej Smyk, MD, global medical director of Neurology & Immunology at Merck, findings revealed an improvement in MS Quality of Life (MSQoL-54) scores, both in the physical (P = .003) and mental health (P <.0001) components, for those on cladribine over the 4-year period compared with the parent study baseline using the total population (n = 265).

Presented at the 2025 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, held February 27-March 1 in West Palm Beach, Florida, the data also showed numerically higher improvements in MSQoL-54 scores among treatment-naïve patients (n = 70) compared with treatment-experienced participants (n = 195) across both physical and mental health components. Improvements in MSQoL-54 scores at 2 years, assessed using repeated mixed-effects linear regression, were sustained through the treatment-free years 3-4 of the extension study.

Over the 4-year treatment period, treated patients continued to show stable scores on various parameters of the Brief International Cognitive Assessment for MS (BICAMS), including Symbol Digit Modalities Test (SDMT), California Verbal Learning Test (CVLT-II), and Brief Visuospatial Memory Test-Revised (BVMT-R). Using Pearson product-movement correlation coefficient, MSQoL-54 and BICAMS components were correlated at week 48, suggesting that better physical and mental health are related to better cognitive function in patients with relapsing MS treated with cladribine.

Cladribine, a disease-modifying treatment, was approved in 2019 as a high-efficacy, immunosuppressive medication for relapsing MS. The treatment is a purine nucleoside analogue that interferes with DNA synthesis, leading to a depletion of B and T lymphocytes. Its action helps modulate the immune response by reducing the pool of lymphocytes implicated in MS-related inflammation, while largely sparing other immune cells. This targeted immunosuppression provides long-lasting effects with intermittent dosing.

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Prior to the extension, the CLARIFY-MS parent study (NCT03369665) first highlighted the therapeutic effects of cladribine tablets on HRQoL and cognition. Post-hoc data from the parent study presented at the 2023 ACTRIMS Forum included 399 individuals who completed BICAMS at 12 and 24 months. At 24 months of treatment, patients demonstrated stable cognitive function, including measures of processing and motor speed, verbal and visuospatial learning, and aspects of memory.²

Overall, the median SDMT scores at baseline were 7.0 (range, 3-17) and remained in that range at the 12- (median, 7.0; range, 3-18) and 24-month (median, 7.0; range, 3-18) time points. Scaled CLVT-II and BVMT-R scores increased slightly from baseline (CLVT-II: median, 10.0; range, 2-18; BVMT-R: median, 8.0; range, 2-18) to month 12 (CLVT-II: median, 11.0; range, 2-18; BVMT-R: median, 9.0; range, 2-18). These increases were sustained through month 24. Notably, investigators found no correlation between annualized percentage brain volume change (PBVC) from baseline to month 24 and BICAMS parameter changes (SDMT, r = 0.11; CVLT-II, r = .17; BVMT-R, r = .07).

In late-2024, NeurologyLive® launched a panel discussion highlighting progression independent of relapses (PIRA) and cognitive functions in MS, with a special episode focused on the CLARIFY-MS extension. In the clip below, panelists Gabriel Pardo, MD, FAAN, and Martin Belkin, DO, highlighted the potential of early treatment to preserve cognitive capabilities in patients with MS. The duo also discussed the need for cognitive assessments in monitoring disease progression and tailoring patient management.

Click here for more ACTRIMS Forum content.

REFERENCES
1. Langdon D, Brochet B, Havrdova EK, et al. P321. Improvements in Health-related Quality of Life and Preserved Cognitive Function in Patients With Relapsing Multiple Sclerosis: 4‑year Results From the CLARIFY-MS Extension Study. Presented at: 2025 ACTRIMS Forum; February 27-March 1; West Palm Beach, FL. ABSTRACT P321.
2. Langdon D, Brochet B, Havrdova EK, et al. Stabilization of cognitive function in patients with highly active relapsing multiple sclerosis treated with cladribine tablets during the 2-year CLARIFY-MS study. Presented at: 2023 ACTRIMS Forum; February 23-25; San Diego, CA. Abstract P090.