Efficacy and safety of Cladribine as a therapeutic option in multiple sclerosis patients over 50 years of age: A real-world study

Abstract

Background: Despite an aging multiple sclerosis (MS) population, clinical outcomes and long-termeffects of disease-modifying therapies in patients aged ≥50 years remain under-studied.

Objective: To compare the efficacy and safety of cladribine in relapsing-remitting MS (RRMS) patients aged <50 versus ≥50 years.

Methods: In this retrospective, observational multicenter study, 366 RRMS patients treated with cladribine (cumulative dose 3.5 mg/kg) were included. Patients were stratified by age at treatment initiation (<50 years, n = 317; ≥50 years, n = 49). Outcomes included annualized relapse rate (ARR), MRI activity, percentage of patients without EDSS progression, and no evidence of disease activity (NEDA-3) at 12 and 24 months. Safety endpoints encompassed lymphocyte nadirs, infection, and malignancy rates.

Results: At baseline, the ≥50-year cohort had longer disease duration (9.8 ± 7.9 vs. 6.6 ± 5.3 years; p < 0.001) and higher EDSS (2.6 ± 1.6 vs. 1.7 ± 1.6; p = 0.001). Eighteen patients aged <50 years (5.7 %) discontinued cladribine before the second course due to breakthrough clinical or radiological activity; all patients ≥50 years completed both courses. After treatment, ARR was lower in the older cohort (0.02 vs. 0.11; p = 0.001). Percentage of patients free of EDSS progression was similar in both groups (97.3 ± 16.2 in <50 years versus 95.9 ± 20 in ≥50 years p = 0.6). NEDA-3 rates at 12 months were 73.2 % (<50 years) versus 77.6 % (≥50 years; p = 0.53) and at 24 months were 90.5 % versus 98.0 % (p = 0.31). Treatment failure occurred in 8.1 % of patients aged <50 years versus 3.0 % of those aged ≥50 years (p = 0.47). Lymphocyte nadirs were similar in both groups. Only one <50 year patient developed grade 4 lymphopenia. Infection (8.1 % vs. 2.3 %; p = 0.21) and malignancy rates (2.0 % vs. 0.6 %; p = 0.86) were similar between groups.

Conclusions: Cladribine demonstrated sustained efficacy and a favorable safety profile in RRMS patients across age groups. The ≥50-year cohort showed a significantly lower ARR and no early treatment discontinuations due to clinical or radiological activity. These findings support its utility in the management of older patients with RRMS.