Lucchini M, Borriello G, Haggiag S, Nicoletti CG, Fantozzi R, Buscarinu MC, Ferrazzano G, Cortese A, Marinelli F, Monteleone F, Centonze D, Conte A, Ferraro E, Gasperini C, Marfia GA, Pozzilli C, Salvetti M, Barbuti E, Bellucci G, Bianco A, Carlomagno V, Cruciani A, De Giglio L, Dionisi C, Ianniello A, Malimpensa L, Nasello M, Nociti V, Prosperini L, Tortorella C, Mirabella M. Real-world experience with cladribine tablets in people with multiple sclerosis: effectiveness data from a multicenter Italian study. Ther Adv Neurol Disord. 2025 Dec 26;18:17562864251360047.
Background: Cladribine (CLAD) stands as an oral disease modifying treatment (DMT) for multiple sclerosis (MS) patients, distinguished by its unique dosing regimen and mechanism of action. However, real-world data on its effectiveness remain limited, particularly regarding the clinical and therapeutical management beyond the 2-year treatment schedule.
Objectives: The aim of our study was to explore the effectiveness profile of CLAD in individuals with MS (pwMS). We assessed the proportion of patients achieving no evidence of disease activity (NEDA-3) status and identified variables associated with better outcomes.
Design: In this retrospective study (looking back on information), we collected clinical and magnetic resonance imaging (MRI) data of MS patients across 10 MS Clinics in Central Italy who started CLAD between 2018 and 2023.
Methods: We evaluated the annualized relapse rate (ARR) during treatment, and the proportion of patients who experienced relapses, radiological activity, and confirmed disability progression. Additionally, we estimated the proportion of patients achieving NEDA-3 among those with a minimum follow-up of 3 months and explored baseline variables associated with NEDA status.
Results: We collected data from 1094 patients with a mean follow-up of 25.1 months, of whom 79% completed the second CLAD cycle. The mean age was 37.7 years (SD 9.7), and the mean disease duration was 6.5 years, with 40.5% being treatment naïve. Despite a significant reduction of the ARR from 0.91 to 0.04 (p < 0.01) following CLAD treatment, 8.9% of patients presented at least one relapse, while 22.0% and 7.9% of patients experienced radiological activity (So this is better than most drugs it says that it is not infalllible. We have often thought that there can be underdosing especially in cycle 2 where low lymphocyte levesl means they don’t dose) or disability progression, respectively. Across the entire study cohort, 70.2% of patients maintained the NEDA-3 status (Better than alemtuzumab). Younger age (HR = 0.98, p < 0.001) and higher expanded disability status scale score (HR = 1.11, p = 0.049) were associated with a higher risk of not achieving the NEDA-3 status (Yep this is a common risk factors seen with other agents so nothing new). Additionally, we included 131 patients who were older than 50 years at the time of CLAD initiation. Among the cohort, 116 patients switched to another DMT after CLAD, primarily anti-CD20 monoclonal antibodies following disease reactivation (It’s a natural switch but it is funny that with alemtuzumab…the solution is redose but with cladribine this dose not really happen and is probably a product of Merck stopping the extension study…what a mistake that was)
Conclusion: This postmarketing experience confirms the effectiveness of CLAD in the treatment of pwMS, with a significant reduction in ARR and a high proportion of patients remaining free from disease activity. By contrast, some patients required an escalation strategy mainly with anti-CD20 monoclonal antibodies because of persisting disease activity.
Source: multiple-sclerosis-research.org