Cladribine Maintains Efficacy, Safety Profile in Older Patients With Multiple Sclerosis

Newly reported findings from the Aging study, a 24-month observational, single-arm, real-world, phase 4 trial, showed that cladribine (Mavenclad; EMD Serono), an FDA-approved disease-modifying therapy for relapsing multiple sclerosis (RMS), maintained its favorable risk-benefit profile in older patients aged 65 and up. All told, the findings support the therapeutic value of cladribine in older patients with RMS, regardless of age at treatment initiation.

This post-hoc analysis, led by Joshua Katz, MD, director of The Elliot Lewis Center for Multiple Sclerosis Care, was presented as a poster at the 2026 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), held February 5-7 in San Diego, California. Of 115 patients included (mean age, 60.8 years), 84 (73.0%) were less than 65 years of age and 31 (27.0%) were older than that mark.

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). In addition, regardless of age, the discontinuation treatment rate remained low as well (total study population: 7.8%; <65 y: 8.3%; ≥65 y: 6.5%).

Cladribine, an oral immune reconstitution therapy, was approved in the United States in 2019 as a disease-modifying treatment for patients with RMS. Mechanistically, it is a purine nucleoside analog that selectively reduces B and T lymphocytes through DNA disruption, leading to a transient but targeted immune depletion followed by gradual immune reconstitution. To date, there have been a small handful of studies looking at the therapy in older patients with the disease.

In terms of safety, adverse event (AEs) rates remained relatively consistent across age groups (total study population: 69.6%; <65 y: 71.4%; ≥65 y: 64.5%) and median lymphocyte counts were stable by month 24 (total study population: 0.79×10⁹ cells/L, <65y: 0.80×10⁹ cells/L, ≥65y: 0.67×10⁹ cells/L). Notably, the rates of serious AEs also were low across all age groups (total study population: 7.0%, <65y: 7.1%, and ≥65y: 6.5%).

Across the study population, adverse events were mostly mild to moderate, with lymphopenia (44.3%), COVID-19 (13.0%), and urinary tract infections (6.1%) reported most often. Notably, adults aged 65 and older had lower rates of these events than younger patients: lymphopenia (38.7% vs 46.4%), COVID-19 (9.7% vs 14.3%) and UTI (3.2% vs 7.1%). Above all, no new safety signals, malignancies, opportunistic infections including progressive multifocal leukoencephalopathy, or deaths were observed.

This was not the first time cladribine had been examined in older patients with MS. In 2025, a real-world study published in the Journal of the Neurological Sciences highlighted the treatment’s sustained efficacy and favorable safety profile in patients aged 50 years and older. The trial, which included 366 patients with relapsing-remitting MS, looked at outcomes like ARR, MRI activity, percentage of patients without Expanded Disability Status Scale (EDSS) progression, and no evidence of disease activity (NEDA).²

In that study, post-treatment analyses showed favorable disease control across age groups, with the older cohort demonstrating a lower annualized relapse rate than younger patients (0.02 vs 0.11; P = 0.001). The proportion of patients free from EDSS progression was comparable between groups, at 97.3% in those younger than 50 years and 95.9% in those aged 50 years and older (P = 0.6). NEDA-3 status was achieved at similar rates at 12 months (73.2% vs 77.6%; P = 0.53) and remained high at 24 months (90.5% vs 98.0%; P = 0.31) in younger versus older patients, respectively. Treatment failure was numerically less frequent in the older group (3.0% vs 8.1%), though this difference was not statistically significant (P = 0.47).

Click here for more ACTRIMS 2026 coverage.

REFERENCES
1. 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.
2. Piedrabuena MA, Correale J, Silva B, et al. Efficacy and safety of Cladribine as a therapeutic option in multiple sclerosis patients over 50 years of age: A real-world study. Journal of Neurological Sciences. 2025;15:478. doi:10.1016/j.jns.2025.123727