Is Cladribine a Suitable Strategy after Natalizumab in MS?
Real-world Outcomes are reported here. What next if people have to switch from natalizumab and this study looks at cladribine. It is OK but we know that cladribine takes 1-2 months to optimally work compared to say a CD20 depleting agent that can kill most B cells within a day. We know that if you wait too long to get a DMT started after natalizumab there is a risk that disease comes back with a vengance. This known as Rebound. In this study they had a wash out on average about 75 day before switching and this is therefore 10 weeks and the drug action will have worn off. Leading to disease breakthrough this occurred in about half the people in the study. So work is needed how to optimise this to reduce the time between switch and start new treatment
Marta Vachova1, Dominika Stastna2, Jiri Drahota3, Pavel Potuznik4, Radek Ampapa5, Michal Dufek6, Marketa Grunermelova7, Eva Kubala Havrdova2, Jana Houskova8, Pavel Hradilek9, Jana Libertinova10, Alena Martinkova11, Zbysek Pavelek12, Marek Peterka4, Eva Recmanova13, Matous Rous14, Zuzana Rous14, Ivana Stetkarova15, Pavel Stourac16, Dana Horakova2, Gregor Fistravec17
1KZ a.s., Hospital Teplice, 2General University Hospital in Prague, 3ReMuS Registry, 4Faculty of medicine and University Hospital in Pilsen, 5Neurologicka Klinika Jihlava, 6First department of Neurology, Masaryk University, St.Anneś University Hospital, 7Thomayer Hospital, 8Hospital Ceske Budejovice, 9University Hospital Ostrava, 102nd Faculty of Medicine, Charles University in Prague and Motol, 11Hospitals of the Pardubice Region, 12Charles University in Prague, Faculty of Medicine and University Hospital Hradec Kralove, 13Tomas Bata Regional Hospital, 14Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, 15Charles University, Third Faculty of Medicine, Department of University, 16University Hospital Brno, Neurology Clinic, 17Registr ReMuS
Objective:To assess both short and long-term clinical disease control after switching from natalizumab to cladribine in people with multiple sclerosis (pwMS) in real-world practice.
Background:Natalizumab provides robust disease control; however, prolonged exposure and JCV seropositivity limit long-term use due to PML risk. When JCV status changes—or other concerns arise—pwMS often require a switch, yet there is no consensus on the optimal exit strategy. Cladribine tablets can be initiated soon after natalizumab discontinuation but have a gradual onset of action. Real-world evidence on whether this approach preserves clinical control in the post-natalizumab remains limited.
Design/Methods:We performed a retrospective cohort study using data from the Czech national MS registry (ReMuS; cut-off 30 June 2025). Adults with relapsing MS who discontinued natalizumab and subsequently initiated cladribine were included; the last natalizumab dose served as baseline. We described baseline characteristics, JCV status, clinical MS activity, and the interval between the last natalizumab and initiation of cladribine (washout).
Results:We included 52 pwMS (female 79%; median age [Q1, Q3] 41.3 [33.6, 50.0] years; disease duration 14.6 [8.3, 20.4] years; EDSS 3.5 [2.5, 5.0]), with median natalizumab exposure 1.8 (0.7, 3.5) years and follow-up 4.1 (2.0, 5.5) years. At baseline, 77% were JCV positive, 40% underwent relapse within the last year. The median washout was 75 (48, 145) days. Early relapse (within a year after baseline) occurred in 40%. Median time to relapse was 281 days (148, 623). Among 39 pwMS with 2-year follow-up, median EDSS progressed from 3.5 (2.5, 5.0) to 4.0 (2.5, 5.5), 3-months CDW occurred in 18%, PIRA in 5.1%. No cases of PML were recorded.
Conclusions:With median 75-day washout between natalizumab and cladribine, 40% experienced relapse within one year. Prolonged washout periods may have contributed to this reactivation rate, warranting further investigation to establish transition protocols.
10.1212/WNL.0000000000213265
Source: multiple-sclerosis-research.org