Cladribine treatment in pediatric-onset multiple sclerosis: real-world clinical outcomes and safety insights

Introduction Pediatric-onset multiple sclerosis (POMS) poses unique therapeutic challenges due to high inflammatory activity, early cognitive and psychosocial impact, and difficulties with long-term treatment adherence. This retrospective cohort study evaluated the real-world safety and clinical outcomes of cladribine tablets compared with standard disease-modifying therapies (DMTs) in children and adolescents with POMS. Methods A retrospective cohort of 47 POMS patients followed at two tertiary neuroimmunology centers was included: 31 received cladribine and 16 other DMTs. Inclusion required at least two years of continuous therapy and annual MRI monitoring. The control group comprised patients who remained on standard DMTs due to stable or well-tolerated disease, while exclusion criteria included prior use of high-potency biological therapies, specifically natalizumab or anti-CD20 agents. Clinical and radiological outcomes were analyzed using standard statistical tests and mixed-effects models. Results Mean age at onset was 15.1 ± 2.5 years in the cladribine group and 13.8 ± 2.2 years in controls. Baseline disease duration was longer among cladribine-treated patients (3.8 ± 3.4 vs. 2.3 ± 1.8 years). NEDA rates were comparable between groups at Year 1. Relapse rates evolved differently over time (Group × Year interaction p = 0.028), reflecting differences in longitudinal patterns rather than a direct comparison of treatment efficacy. MRI and OCT measures showed no significant differences between groups. Withdrawal rates were lower with cladribine (9.4% vs. 52.6%), and no severe adverse events occurred. Conclusion Cladribine demonstrated favorable safety, high adherence and comparable outcomes to standard DMTs, supporting its feasibility as an off-label option for selected pediatric patients.