Long‐Term Disease Control Following Completion of Cladribine Treatment in Multiple Sclerosis: Extended Follow‐Up of the CladStop Cohort

Abstract

Background: Long‐term disease control after the standard two‐year cladribine course in multiple sclerosis (MS) remains insufficiently characterized in real‐world settings. We evaluated disease control, treatment re‐initiation, and safety during extended follow‐up of the multicenter CladStop cohort after treatment completion. Methods: We included 204 patients with relapsing MS who completed the approved two‐year cladribine regimen and had ≥ 6 months of follow‐up after treatment completion. Time zero (“CladStop”) was defined as 24 months after first cladribine dosing. Co‐primary endpoints were time to loss of no evidence of disease activity (NEDA‐3) and annualized relapse rate (ARR) after CladStop. Kaplan–Meier analyses, multivariable Cox models, and mixed‐effects Poisson regression were applied. Results: Mean follow‐up after CladStop was 44.2 ± 8.6 months. Overall, 81/204 patients (39.7%) lost NEDA‐3. NEDA‐3 survival was 82.8% (95% CI 77.8–88.2) at 12 months, 69.6% (95% CI 63.6–76.2) at 24 months, and 56.4% (95% CI 49.2–64.8) at 48 months. Forty‐two patients (20.6%) relapsed, with an overall ARR of 0.06 (95% CI 0.04–0.08). Relapse rates decreased over time (rate ratio/year 0.74, 95% CI 0.55–0.999; p = 0.044). MRI activity occurred in 29.9% of patients and 6‐month confirmed disability progression in 7.4%. A new DMT was initiated in 40.7% of patients. Relapses during treatment predicted earlier DMT initiation. Conclusions: Disease control remained durable in many patients after completion of cladribine treatment. However, over 40% initiated subsequent DMT during follow‐up, indicating that prolonged treatment‐free remission is not universal. Disease reactivation was driven mainly by inflammatory activity rather than disability worsening.