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

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.

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Journal
European Journal of Neurology
Published
2026-10-30
DOI
https://doi.org/10.1111/ene.70763
Primary Topic
Multiple Sclerosis Research Studies
Type
article
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article

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

Angela Albanese, Gianmarco Abbadessa, Diego Centonze, Roberta Fantozzi et al.
6 links
European Journal of Neurology
Multiple Sclerosis Research Studies
article

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

Angela Albanese, Gianmarco Abbadessa, Diego Centonze, Roberta Fantozzi, Diana Ferraro, Girolama Alessandra Marfia, Jessica Frau, Paolo Immovilli, Irene Schiavetti, Alessio Signori, Elisabetta Signoriello, Doriana Landi, Claudio Gobbi, Lorena Lorefice, Leonardo Malimpensa, Massimiliano Di Filippo, Simona Bonavita, Maria Pia Sormani, Francesca Ruscica, Flora Govone, Chiara Zecca, Rosa Iodice, Cinzia Cordioli, Giacomo Lus, Sonia Di Lemme, Eleonora E. Cocco, Livia Pasquali, Anna M. Repice, Maria Teresa Ferrò, CladStop Study Group
article en

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.

European Journal of NeurologyVol. 33(11)
University of Pisa (IT), University of Rome Tor Vergata (IT), University of Cagliari (IT), University of Campania "Luigi Vanvitelli" (IT), University of Perugia (IT), Istituto Neurologico Mediterraneo (IT), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Azienda Ospedaliero-Universitaria di Modena (IT), Azienda Ospedaliero-Universitaria Careggi (IT), Federico II University Hospital (IT), Azienda Ospedaliera Universitaria Università degli Studi della Campania Luigi Vanvitelli (IT), Fondazione Istituto G. Giglio di Cefalù (IT), Guglielmo da Saliceto Hospital (IT), IRCCS Azienda Ospedaliera Metropolitana (IT), Università della Svizzera italiana (CH), University of Naples Federico II (IT), University of Genoa (IT), Sapienza University of Rome (IT)
Good health and well-being
Openalex Percentile: Top 12%
Multiple Sclerosis Research Studies
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