Newly reported findings suggest that cladribine, a disease-modifying therapy for relapsing multiple sclerosis (RMS), continues to demonstrate both effectiveness and a favorable safety profile in older patients. The data, presented at the 2026 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum in San Diego, California, offer reassurance regarding the use of cladribine in individuals aged 65, and older.
The findings stem from the ‘Aging’ study, a 24-month observational, single-arm, real-world, phase 4 trial. Researchers analyzed data from 115 patients with a mean age of 60.8 years, with a substantial proportion (73.0%, or 84 individuals) under the age of 65 and the remaining 27.0% (31 individuals) aged 65 and above. The analysis focused on annualized relapse rates (ARRs) as the primary endpoint.
The study revealed consistently low ARRs across all age groups. Specifically, patients aged 50 and above experienced an ARR of 0.07 (95% Confidence Interval [CI], 0.03-0.12), those 65 and younger had an ARR of 0.10 (95% CI, 0.03-0.16), and those over 65 exhibited an ARR of 0.02 (95% CI, -0.02 to 0.05). Importantly, the rate of treatment discontinuation remained low throughout the study period, at 7.8% 8.3% for those under 65, and 6.5% for those 65 and older.
Cladribine, marketed as Mavenclad, is an oral immune reconstitution therapy approved by the FDA in 2019 for the treatment of RMS. Its mechanism of action involves selectively reducing both B and T lymphocytes by disrupting DNA, leading to a temporary but targeted depletion of the immune system followed by a gradual recovery.
In terms of safety, adverse event (AE) rates were comparable across the different age groups: 69.6% in the total study population, 71.4% in those under 65, and 64.5% in those 65 and older. Median lymphocyte counts remained stable at month 24, with values of 0.79×109 cells/L for the total population, 0.80×109 cells/L for those under 65, and 0.67×109 cells/L for those 65 and older. Rates of serious adverse events were also low and consistent across all age groups (7.0% 7.1% under 65, and 6.5% aged 65 and older).
The most frequently reported adverse events were lymphopenia (44.3%), COVID-19 (13.0%), and urinary tract infections (6.1%). Interestingly, individuals aged 65 and older experienced lower rates of these events compared to younger patients: lymphopenia (38.7% vs 46.4%), COVID-19 (9.7% vs 14.3%), and urinary tract infections (3.2% vs 7.1%). No new safety signals, malignancies, opportunistic infections – including progressive multifocal leukoencephalopathy – or deaths were observed during the study.
These findings build upon previous research examining cladribine’s use in older patients. A real-world study published in 2025 in the Journal of the Neurological Sciences also demonstrated sustained efficacy and a favorable safety profile in patients aged 50 years and older. That study, which included 366 patients with relapsing-remitting MS, assessed outcomes such as ARR, MRI activity, progression on the Expanded Disability Status Scale (EDSS), and no evidence of disease activity (NEDA).
The 2025 study revealed favorable disease control across all age groups, with the older cohort exhibiting a lower annualized relapse rate compared to younger patients (0.02 vs 0.11; P = 0.001). The proportion of patients free from EDSS progression was comparable between the groups (97.3% in those under 50 and 95.9% in those 50 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, though not statistically significantly, less frequent in the older group (3.0% vs 8.1%; P = 0.47).
The research, led by Joshua Katz, MD, director of The Elliot Lewis Center for Multiple Sclerosis Care, adds to the growing body of evidence supporting the therapeutic value of cladribine in older patients with RMS, regardless of the age at which treatment is initiated.
