From Clinical Trial Efficacy to Real-World Effectiveness and Safety: Two-Year Outcomes of Cladribine in...

Background/Objectives: Cladribine is a high-efficacy immune reconstitution therapy for relapsing multiple sclerosis, but additional real-world data remain valuable, particularly from single-center cohorts with combined clinical, radiological, and laboratory follow-up. This study aimed to evaluate the 24-month effectiveness and safety of cladribine in patients with relapsing-remitting multiple sclerosis (RRMS), with a particular focus on no evidence of disease activity (NEDA-3) and lymphopenia. Methods: This retrospective single-center observational cohort study included adults with RRMS treated with cladribine who had at least 24 months of clinical and MRI follow-up. NEDA-3 was defined as the absence of clinical relapses, disability progression, and MRI activity. Brain MRI was performed at 6, 12, and 24 months. Absolute lymphocyte counts were monitored longitudinally, and lymphopenia was graded according to standard criteria. Results: A total of 71 patients were included. NEDA-3 was achieved in 61 patients (85.9%) at 12 months and 50 patients (70.4%) at 24 months. No demographic or baseline clinical variable was independently associated with NEDA-3 at either time point. Lymphopenia occurred in 53 patients (74.6%), including grade 1 in 14 (19.7%), grade 2 in 23 (32.4%), grade 3 in 14 (19.7%), and grade 4 in 2 (2.8%). One patient developed herpes zoster infection during follow-up. Conclusions: Cladribine demonstrated durable effectiveness and a manageable safety profile over 24 months in a real-world RRMS population. The close alignment between our findings and those reported in pivotal clinical trials underscores the external validity of cladribine efficacy beyond controlled study environments. These data provide valuable real-world evidence bridging the gap between controlled research settings and everyday patient care, thereby strengthening the evidence base for cladribine in contemporary MS management.