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Peer-reviewedCC BY-NC-NDEuropean journal of neurology

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

  • Irene Schiavetti1,2
  • Alessio Signori1,2
  • Angela Albanese1
  • Jessica Frau3,4
  • Eleonora Cocco3,4
  • Lorena Lorefice3
  • Sonia di Lemme5
  • Roberta Fantozzi5
  • Diego Centonze5,6
  • Doriana Landi5,7
  • Girolama Marfia5,7
  • Elisabetta Signoriello8
18 more authors
  • Giacomo Lus8
  • Chiara Zecca9,10
  • Claudio Gobbi9,10
  • Rosa Iodice11
  • Leonardo Malimpensa12
  • Cinzia Cordioli13
  • Diana Ferraro14
  • Francesca Ruscica15
  • Livia Pasquali16
  • Anna Repice17
  • Paolo Immovilli18
  • Maria Teresa Ferrò19
  • Simona Bonavita20
  • Massimiliano Di Filippo21
  • Gianmarco Abbadessa22
  • Flora Govone23
  • Maria Pia Sormani1,2
  • CladStop Study Group
23 affiliations
  1. 1Department of Health Sciences, University of Genoa, Genova, Italy.
  2. 2IRCCS Azienda Ospedaliera Metropolitana, Genova, Italy.
  3. 3Centro Sclerosi Multipla Ospedale Binaghi Cagliari, Azienda Sanitaria Locale (ASL) Cagliari, Cagliari, Italy.
  4. 4Dipartimento Scienze Mediche e Sanità Pubblica, Università di Cagliari, Cagliari, Italy.
  5. 5Unit of Neurology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Pozzilli, Italy.
  6. 6Department of Systems Medicine, Tor Vergata University, Rome, Italy.
  7. 7Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, Tor Vergata University, Rome, Italy.
  8. 8Centro Sclerosi Multipla, II Clinica Neurologica, Università della Campania Luigi Vanvitelli, Naples, Italy.
  9. 9Multiple Sclerosis Center, Neurocenter of Southern Switzerland, EOC, Lugano, Switzerland.
  10. 10Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.
  11. 11Clinica Neurologica, DSNRO Università Federico II di Napoli, Napoli, Italy.
  12. 12Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy.
  13. 13Centro Sclerosi Multipla, Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili di Brescia, Montichiari, Italy.
  14. 14Department of Neurosciences, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.
  15. 15Unità operativa di Neurologia, Fondazione Istituto G.Giglio, Cefalù, Italy.
  16. 16Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
  17. 17Department of Neurology 2, Careggi University Hospital, Florence, Italy.
  18. 18Neurology Unit, Emergency Department, Guglielmo da Saliceto Hospital, Piacenza, Italy.
  19. 19Neurological Unit, Cerebrovascular Department, Neuroimmunology, Center for Multiple Sclerosis, ASST Crema, Crema, Italy.
  20. 20Dipartimento di Scienze Mediche e Chirurgiche Avanzate, Università della Campania Luigi Vanvitelli, Naples, Italy.
  21. 21Clinica Neurologica, Dipartimento di Medicina e Chirurgia, Università di Perugia, Perugia, Italy.
  22. 22I Division of Neurology, University of Campania "Luigi Vanvitelli", Naples, Italy.
  23. 23Centro Sclerosi Multipla-Neurologia di Mondovì, Cuneo, Italy.
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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.

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Cite

BibTeXRIS
BibTeX
@article{schiavetti2026longterm,
  title = {{Long-Term Disease Control Following Completion of Cladribine Treatment in Multiple Sclerosis: Extended Follow-Up of the CladStop Cohort.}},
  author = {Irene Schiavetti and Alessio Signori and Angela Albanese and Jessica Frau and Eleonora Cocco and Lorena Lorefice and Sonia di Lemme and Roberta Fantozzi and Diego Centonze and Doriana Landi and Girolama Marfia and Elisabetta Signoriello and Giacomo Lus and Chiara Zecca and Claudio Gobbi and Rosa Iodice and Leonardo Malimpensa and Cinzia Cordioli and Diana Ferraro and Francesca Ruscica and Livia Pasquali and Anna Repice and Paolo Immovilli and Maria Teresa Ferrò and Simona Bonavita and Massimiliano Di Filippo and Gianmarco Abbadessa and Flora Govone and Maria Pia Sormani and CladStop Study Group},
  journal = {European journal of neurology},
  year = {2026},
  month = oct,
  doi = {10.1111/ene.70763},
  url = {https://europepmc.org/article/MED/42963188},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Long-Term Disease Control Following Completion of Cladribine Treatment in Multiple Sclerosis: Extended Follow-Up of the CladStop Cohort.
AU  - Irene Schiavetti
AU  - Alessio Signori
AU  - Angela Albanese
AU  - Jessica Frau
AU  - Eleonora Cocco
AU  - Lorena Lorefice
AU  - Sonia di Lemme
AU  - Roberta Fantozzi
AU  - Diego Centonze
AU  - Doriana Landi
AU  - Girolama Marfia
AU  - Elisabetta Signoriello
AU  - Giacomo Lus
AU  - Chiara Zecca
AU  - Claudio Gobbi
AU  - Rosa Iodice
AU  - Leonardo Malimpensa
AU  - Cinzia Cordioli
AU  - Diana Ferraro
AU  - Francesca Ruscica
AU  - Livia Pasquali
AU  - Anna Repice
AU  - Paolo Immovilli
AU  - Maria Teresa Ferrò
AU  - Simona Bonavita
AU  - Massimiliano Di Filippo
AU  - Gianmarco Abbadessa
AU  - Flora Govone
AU  - Maria Pia Sormani
AU  - CladStop Study Group
PY  - 2026
DA  - 2026/10/30
JO  - European journal of neurology
DO  - 10.1111/ene.70763
UR  - https://europepmc.org/article/MED/42963188
AB  - 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.
SN  - 1351-5101
SN  - 1468-1331
ER  -