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.

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).

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.