Cladribine Tablets Show Ability to Improve or Stabilize Cognitive Function in Patients With Relapsing Multiple Sclerosis

Patients with relapsing multiple sclerosis (RMS) treated with short-course cladribine tablets (CladT; Mavenclad; EMD Serono), an FDA-approved disease-modifying therapy for RMS, showed improved or stabilized cognitive processing speed (CPS) according to the Symbol Digit Modalities Test (SDMT) at 4 years of follow-up, according to pooled data from the CLARIFY-MS extension (NCT04776213) and MAGNIFY-MS extension (NCT04783935) clinical studies.¹ The data were presented at the 2026 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), held February 5-7 in San Diego, California.

According to the ACTRIMS abstract, the analysis included 280 patients from CLARIFY-MS extension and 219 patients from MAGNIFY-MS extension, a total of 499 patients who had at least 4 years of follow-up. At 48 months, the whole group showed an improvement of +1.79 points (P<.0001) on SDMT from baseline. In addition, the subgroup of patients aged less than 50 years showed a +2.22 point improvement on SDMT (P<.0001). An improvement of +0.81 points (P=0.7806) was also seen in the subgroup of patients aged more than 50 years, but this finding was not statistically significant.

With a ≥8-point change in SDMT threshold for stability, 86.6% of the whole group showed either improvement or stability at 4 years compared to baseline and only 12.9% showed worsening. On the other hand, with a ≥4-point change in SDMT threshold for stability, 74.4% of the whole group showed either improvement or stability at 4 years compared to baseline and 25.2% showed worsening. First author Bruno Brochet, MD, an emeritus professor of neurology at Université of Bordeaux, France, and colleagues noted that the group of patients aged less than 50 years had a higher proportion of improvement/stability than patients aged more than 50 years at both the ≥8-point threshold (87.4% vs 81.6%) and ≥4-point threshold (75.3% vs 68.3%). Likewise, the group of patients with baseline SDMT scores of less than 53 had a higher proportion of improvement/stability than patients with baseline SDMT scores of 53 or greater at both the ≥8-point threshold (89.6% vs 84.6%) and ≥4-point threshold (80.1% vs 69.6%).

“Overall, most people with RMS treated with CladT either improved or had stabled cognitive function,” Brochet and colleageus wrote in their ACTRIMS poster.¹ “Clinically meaningful improvements or stability in CPS were observed over 4 years, particularly in younger people with RMS (less than 50 years) and those with baseline SDMT score below 53 points. These findings suggest long-term benefits of CladT beyond its effects on conventional disability indices, especially when initiated earlier in the disease course.”

Notably, data from a separate poster presentation at ACTRIMS showcased findings from the Aging study, a 24-month observational, single-arm, real-world, phase 4 trial, demonstrating that CladT maintained its favorable risk-benefit profile in older patients aged 65 and up.² After 24 months of treatment, annualized relapse rates (ARRs), the primary end point, were low across all study groups, regardless of age. This included those above 50 (0.07; 95% CI, 0.03-0.12), 65 and younger (0.10; 95% CI, 0.03-0.16), and those above 65 (0.02; 95% CI, –0.02 to 0.05). Rates of adverse event (AEs) were also found to be relatively consistent across age groups, with a 69.6% AE rate in the total study population, a 71.4% rate in patients aged less than 65 years, and a 64.5% rate in patients aged 65 years or older.

“CladT maintained a favorable benefit-risk profile across older age groups, with sustained effectiveness, comparable safety, and no increase in safety signals observed in patients aged ≥65y versus <65y,” first author Joshua Katz, MD, director of The Elliot Lewis Center for Multiple Sclerosis Care, and colleagues wrote in their abstract.² “These findings support the therapeutic value of CladT in older PwRMS, regardless of age at treatment initiation.”

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REFERENCES
1. Brochet B, Havrdova EK, Selmaj K, et al. P404. Cladribine tablets maintain or improve cognition over 4 years in people with relapsing multiple sclerosis: pooled analyses of the CLARIFY-MS and MAGNIFY-MS extension studies. Presented at: 2026 ACTRIMS Forum; Feb 5-7; San Diego, CA. Abstract P117.
2. Katz J, Hughes B, Gutierrez A, et al. P404. Real-World Effectiveness and Safety of Cladribine Tablets in Older Patients with Relapsing Multiple Sclerosis: Insights from the 'Aging' Study Subgroup Analysis. Presented at: 2026 ACTRIMS Forum; Feb 5-7; San Diego, CA. Abstract P404.