With Alemtuzumab about 50% of people need a thrid dose because of disease breakthrough and only about 50% of them would need a forth course because of disease breakthrough. The result is when there is disease breakthrough another dose was given.
Cladribine development was stopped and after the first year of treatment, there is nothing prescribed for 3 years more but then what?. Disease breakthrough often leads to a switch but why the difference to the alemtuzumab mentaility. In this study from Czechia they looked and after 5 years, over 40% were relapse free but some needed retreatment and that kept disease at bay. It is a shame that the manufacturers dropped the ball and lost the long-term data that would be have guided the retreatment decision. This could make cladribine a very good WHO essential medicine as it is becoming generic all over. This could change the MS World for the better.
Five-by-Five: Nationwide Real-world Outcomes after ≥Five Years of Cladribine With an Age ≥50 Subanalysis
Dominika Stastna1, Marta Vachova2, Jiri Drahota3, Pavel Potuznik4, Radek Ampapa5, Michal Dufek6, Marketa Grunermelova7, Eva Havrdova1, Jana Houskova8, Jana Libertinova9, Alena Martinkova10, Zbyšek Pavelek11, Marek Peterka4, Eva Recmanova12, Zuzana Rous13, Matous Rous13, Ivana Stetkarova14, Pavel Stourac15, Ivana Woznicova16, Dana Horakova1, Gregor Fistravec3.1Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czechia, 2Department of Neurology, KZ a.s., Hospital Teplice, Teplice, Czechia, 3ReMuS, The Czech Republic Multiple Sclerosis Patient Registry, Prague, Czechia, 4Department of Neurology, Faculty of Medicine and University Hospital in Pilsen, Charles University, Plzen, Czechia, 5Department of Neurology, Hospital of Jihlava, Jihlava, Czechia, 6First Department of Neurology, Masaryk University, St. Anne’s University Hospital, Brno, Czechia, 7Department of Neurology, Thomayer Hospital, Prague, Czechia, 8Department of Neurology, Hospital Ceske Budejovice, Ceske Budejovice, Czechia, 9Department of Neurology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czechia, 10Department of Neurology, Hospitals of the Pardubice Region, Hospital of Pardubice, Pardubice, Czechia, 11Department of Neurology, Charles University in Prague, Faculty of Medicine and University Hospital Hradec Kralove, Hradec Kralove, Czechia, 12Department of Neurology, Tomas Bata Regional Hospital, Zlin, Czechia, 13Department of Neurology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czechia, 14Charles University in Prague, Third Faculty of Medicine, Charles University and Hospital Kralovske Vinohrady, Prague, Czechia, 15Department of Neurology, Masaryk University and University Hospital Brno, Brno, Czechia, 16Department of Neurology, University Hospital Ostrava, Ostrava, Czechia
Objective:To assess long-term use of cladribine in people with multiple sclerosis (pwMS), including retreatment efficacy and observations in pwMS aged ≥50 years at baseline (first cladribine tablet) in real-world settings.
Background:While cladribine shows sustained efficacy through 4 years in trials, real-world evidence beyond this timepoint remains limited, particularly retreatment strategies and age-specific outcomes.
Design/Methods:We used data from the Czech national MS registry (ReMuS) and included pwMS who had completed full 2 courses of cladribine by June 30, 2025, with ≥5 years of follow-up. We assessed clinical effectiveness and treatment patterns. Patients were classified as: N (no further treatment), R (retreatment with cladribine), and S (switch to another therapy). We performed exploratory analysis in pwMS aged ≥50.
Results: Of 1,749 pwMS completing 2 cladribine courses, 352 had ≥5-year follow-up (mean ±SD baseline age 37.1±9.3 years, 74% female, 92% pre-treated [14% high-efficacy disease-modifying therapies], EDSS 2.7±1.2). At year 5, 41% remained relapse-free, 89% PIRA-free, and 71% 3-month CDP-free. Groups N/R/S comprised 50.6%/26.1%/23.3% of pwMS, with majority of retreatments occurring in year 5. Among 79 retreated patients with ≥1-year follow-up after retreatment, relapse-free rates increased from 38% in a year pre-retreatment to 85% in a year post-retreatment. In the age ≥50 subgroup (n=33), 67% required no further treatment (vs 49% in <50), only 9.1% switched (vs 25% in <50), and all retreated patients achieved relapse-free status, with other disease characteristics comparable to pwMS aged <50 years.
Conclusions:More than half of pwMS do not require additional treatment 5 years after initiating cladribine tablets, despite not being treatment-naïve. Retreatment appears to be a beneficial strategy, effectively restoring disease control with relapse-free rates increasing from 38% to 85%. PwMS aged ≥50 years showed encouraging patterns consistent with suitability for an exit-strategy subgroup, albeit with interpretation limited by small sample size.
Now off to Spain for the their story
Real Life Effectiveness and Tolerability of Cladribine Tablets (CladT) after Five Years of Treatment
Antonio Pato Pato1, José Ramón Lorenzo González2, Daniel Apolinar García Estévez3, Ana María López Real4, Ana Rodriguez Regal5, Eva Costa Arpin6, María Rodriguez Rodriguez7, Elena Alvarez Rodriguez1, Miguel Alberte Woodgard8, Marta Aguado Valcarcel1, Inés González Suarez1, José María Oscar Prieto Gonzalez8
1Neurology, Complexo Hospitalario de Vigo, 2Neurology, Hospital Povisa de Vigo, 3Neurology, Complexo Hospitalario de Ourense, 4Neurology, Complexo Hospitalario de A Coruña, 5Neurology, Complexo Hospitalario de Pontevedra, 6Neurology, Complexo Hospitalario de Ferrol, 7Neurology, Hospital Universitario Lucus Augusti, 8Neurology, Hospital Clínico Universitario de Santiago de Compostela
Objective:To describe the effectiveness and tolerability of CladT in a clinical practice setting after 5 years of treatment.
Background: Cladribine is an immune reconstitution therapy approved for treating Relapsing-Remitting Multiple Sclerosis. While its efficacy and adverse events aredocumented in randomized controlled trials, additional data from clinical practice is essential.
Design/Methods: Observational, multicenter, retrospective study including patients from 8 hospitals in Spain. Data collected included demographics, disability, relapse rates, gadolinium (Gd)-enhancing lesions, lymphocyte counts, adverse events, and reasons for treatment discontinuation.
Results: A total of 342 patients were included, with an average age of 42.87 years (±10.78), 75.1% were females and 22.2% treatment naïve. The mean disease duration was 9.18 years (±7.7) and the mean of previous treatments 1.26 (±0.95). The average annual relapse rate (ARR) was 0.80 (±0.71), the average EDSS score 1.82 (±1.28) and the average number of Gd-enhancing lesions 1.03 (±2.31). CladT reduced the ARR significantly to 0.17 (±0.42), 0.13 (±0.40), 0.07 (±0.28), 0.13 (±0.37), and 0.05 (±0.22) (p<0.05) and the number of Gd- enhancing lesions to 0.18 (±0.89), 0.16 (±0.77), 0.23 (±1.12), 0.15 (±0.69), 0.35 (±1.67) (p<0.05) over the 5 years. EDSS scores remained stable over the 5-year period (p>0.05). Lymphocyte counts varied from 1368 (±525), 1171 (±524), 1387 (±643), 1480 (±651), 1520 (±618), p<0.05 and adverse events were
reported in 24%, 15%, 15%, 8% and 8% of patients over the 5 years,
respectively, with the most common being fatigue (6.0%), urinary (3.35%) and respiratory infections (3.0%). Additionally, 98.3%, 95.9%, 91.5%, 87.5% and 91.5% of patients remained on treatment after years 1,2,3,4 and 5.
Conclusions: CladT demonstrates effectiveness in real-life setting, indicated by stable EDSS scores and reduced relapse rates and Gd-enhancing lesions. It is well tolerated, with high treatment persistence after 5 years of follow-up.
COI: None really as I get no financial benefit, but am a CladLad as I have supported ProfKs development of cladribine.
Source: multiple-sclerosis-research.org