Real-world experience with cladribine tablets in people with multiple sclerosis: effectiveness data from a multicenter Italian study

Background: Cladribine (CLAD) stands as an oral disease modifying treatment (DMT) for\r\nmultiple sclerosis (MS) patients, distinguished by its unique dosing regimen and mechanism\r\nof action. However, real-world data on its effectiveness remain limited, particularly regarding\r\nthe clinical and therapeutical management beyond the 2-year treatment schedule.\r\nObjectives: The aim of our study was to explore the effectiveness profile of CLAD in individuals\r\nwith MS (pwMS). We assessed the proportion of patients achieving no evidence of disease\r\nactivity (NEDA-3) status and identified variables associated with better outcomes.\r\nDesign: In this retrospective study, we collected clinical and magnetic resonance imaging\r\n(MRI) data of MS patients across 10 MS Clinics in Central Italy who started CLAD between 2018\r\nand 2023.\r\nMethods: We evaluated the annualized relapse rate (ARR) during treatment, and the\r\nproportion of patients who experienced relapses, radiological activity, and confirmed disability\r\nprogression. Additionally, we estimated the proportion of patients achieving NEDA-3 among\r\nthose with a minimum follow-up of 3 months and explored baseline variables associated with\r\nNEDA status.\r\nResults: We collected data from 1094 patients with a mean follow-up of 25.1 months, of\r\nwhom 79% completed the second CLAD cycle. The mean age was 37.7 years (SD 9.7), and the\r\nmean disease duration was 6.5 years, with 40.5% being treatment naïve. Despite a significant\r\nreduction of the ARR from 0.91 to 0.04 (p < 0.01) following CLAD treatment, 8.9% of patients\r\npresented at least one relapse, while 22.0% and 7.9% of patients experienced radiological\r\nactivity or disability progression, respectively. Across the entire study cohort, 70.2% of patients\r\nmaintained the NEDA-3 status. Younger age (HR = 0.98, p < 0.001) and higher expanded\r\ndisability status scale score (HR = 1.11, p = 0.049) were associated with a higher risk of not\r\nachieving the NEDA-3 status. Additionally, we included 131 patients who were older than\r\n50 years at the time of CLAD initiation. Among the cohort, 116 patients switched to another\r\nDMT after CLAD, primarily anti-CD20 monoclonal antibodies following disease reactivation.\r\nConclusion: This postmarketing experience confirms the effectiveness of CLAD in the\r\ntreatment of pwMS, with a significant reduction in ARR and a high proportion of patients\r\nremaining free from disease activity. By contrast, some patients required an escalation\r\nstrategy mainly with anti-CD20 monoclonal antibodies because of persisting disease activity.