{ "abstract": "Background\n\nLong-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\n\nWe 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\n\nMean 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\n\nDisease 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.", "abstract_shown": true, "affiliations": [ "Department of Health Sciences, University of Genoa, Genova, Italy.", "IRCCS Azienda Ospedaliera Metropolitana, Genova, Italy.", "Centro Sclerosi Multipla Ospedale Binaghi Cagliari, Azienda Sanitaria Locale (ASL) Cagliari, Cagliari, Italy.", "Dipartimento Scienze Mediche e Sanità Pubblica, Università di Cagliari, Cagliari, Italy.", "Unit of Neurology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Pozzilli, Italy.", "Department of Systems Medicine, Tor Vergata University, Rome, Italy.", "Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, Tor Vergata University, Rome, Italy.", "Centro Sclerosi Multipla, II Clinica Neurologica, Università della Campania Luigi Vanvitelli, Naples, Italy.", "Multiple Sclerosis Center, Neurocenter of Southern Switzerland, EOC, Lugano, Switzerland.", "Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.", "Clinica Neurologica, DSNRO Università Federico II di Napoli, Napoli, Italy.", "Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy.", "Centro Sclerosi Multipla, Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili di Brescia, Montichiari, Italy.", "Department of Neurosciences, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.", "Unità operativa di Neurologia, Fondazione Istituto G.Giglio, Cefalù, Italy.", "Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.", "Department of Neurology 2, Careggi University Hospital, Florence, Italy.", "Neurology Unit, Emergency Department, Guglielmo da Saliceto Hospital, Piacenza, Italy.", "Neurological Unit, Cerebrovascular Department, Neuroimmunology, Center for Multiple Sclerosis, ASST Crema, Crema, Italy.", "Dipartimento di Scienze Mediche e Chirurgiche Avanzate, Università della Campania Luigi Vanvitelli, Naples, Italy.", "Clinica Neurologica, Dipartimento di Medicina e Chirurgia, Università di Perugia, Perugia, Italy.", "I Division of Neurology, University of Campania \"Luigi Vanvitelli\", Naples, Italy.", "Centro Sclerosi Multipla-Neurologia di Mondovì, Cuneo, Italy." ], "article_type": "research article", "arxiv": null, "author_total": 30, "authors": [ { "affs": [ 0, 1 ], "name": "Irene Schiavetti", "orcid": "0000-0002-5460-2977" }, { "affs": [ 0, 1 ], "name": "Alessio Signori", "orcid": "0000-0001-6289-9144" }, { "affs": [ 0 ], "name": "Angela Albanese" }, { "affs": [ 2, 3 ], "name": "Jessica Frau", "orcid": "0000-0001-9068-9144" }, { "affs": [ 2, 3 ], "name": "Eleonora Cocco", "orcid": "0000-0002-3878-8820" }, { "affs": [ 2 ], "name": "Lorena Lorefice", "orcid": "0000-0003-2050-2908" }, { "affs": [ 4 ], "name": "Sonia di Lemme" }, { "affs": [ 4 ], "name": "Roberta Fantozzi", "orcid": "0000-0002-7527-575X" }, { "affs": [ 4, 5 ], "name": "Diego Centonze", "orcid": "0000-0002-8390-8545" }, { "affs": [ 4, 6 ], "name": "Doriana Landi", "orcid": "0000-0002-3309-8417" }, { "affs": [ 4, 6 ], "name": "Girolama Marfia", "orcid": "0000-0001-5863-7758" }, { "affs": [ 7 ], "name": "Elisabetta Signoriello", "orcid": "0000-0001-5753-6752" }, { "affs": [ 7 ], "name": "Giacomo Lus" }, { "affs": [ 8, 9 ], "name": "Chiara Zecca", "orcid": "0000-0002-9990-3431" }, { "affs": [ 8, 9 ], "name": "Claudio Gobbi", "orcid": "0000-0002-7554-0664" }, { "affs": [ 10 ], "name": "Rosa Iodice", "orcid": "0000-0002-6939-4760" }, { "affs": [ 11 ], "name": "Leonardo Malimpensa", "orcid": "0000-0002-0945-4282" }, { "affs": [ 12 ], "name": "Cinzia Cordioli" }, { "affs": [ 13 ], "name": "Diana Ferraro", "orcid": "0000-0003-4818-3806" }, { "affs": [ 14 ], "name": "Francesca Ruscica" }, { "affs": [ 15 ], "name": "Livia Pasquali", "orcid": "0000-0002-4297-3308" }, { "affs": [ 16 ], "name": "Anna Repice" }, { "affs": [ 17 ], "name": "Paolo Immovilli", "orcid": "0000-0001-9417-3903" }, { "affs": [ 18 ], "name": "Maria Teresa Ferrò" }, { "affs": [ 19 ], "name": "Simona Bonavita", "orcid": "0000-0002-8561-9720" }, { "affs": [ 20 ], "name": "Massimiliano Di Filippo", "orcid": "0000-0002-2645-7477" }, { "affs": [ 21 ], "name": "Gianmarco Abbadessa", "orcid": "0000-0001-8912-3055" }, { "affs": [ 22 ], "name": "Flora Govone" }, { "affs": [ 0, 1 ], "name": "Maria Pia Sormani", "orcid": "0000-0001-6892-104X" }, { "name": "CladStop Study Group" } ], "bibtex": "https://research.draconitic.com/paper/44kds0caj4axt.bib", "cited_by": 0, "doi": "10.1111/ene.70763", "fulltext_url": "https://europepmc.org/articles/PMC13722574", "id": "44kds0caj4axt", "issns": [ "1351-5101", "1468-1331" ], "landing_url": "https://europepmc.org/article/MED/42963188", "language": "eng", "licence": "CC-BY-NC-ND", "licence_label": "CC BY-NC-ND", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Original Article" ], [ "openalex", "2734|Multiple Sclerosis Research Studies" ] ], "openalex": "W7224861736", "pdf_url": "https://europepmc.org/articles/PMC13722574?pdf=render", "pmcid": "PMC13722574", "pmid": "42963188", "published": "2026-10-30", "publisher": "Wiley", "ris": "https://research.draconitic.com/paper/44kds0caj4axt.ris", "sources": [ { "first_seen": "2026-11-02T03:21:21Z", "native_id": "MED:42963188", "source": "europepmc", "url": "https://europepmc.org/article/MED/42963188" }, { "first_seen": "2026-11-04T12:21:22Z", "native_id": "PMC13722574", "source": "pmc", "url": "https://doi.org/10.1111/ene.70763" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2734|Multiple Sclerosis Research Studies", "subfield": "general" } ], "title": "Long-Term Disease Control Following Completion of Cladribine Treatment in Multiple Sclerosis: Extended Follow-Up of the CladStop Cohort.", "title_text": "Long-Term Disease Control Following Completion of Cladribine Treatment in Multiple Sclerosis: Extended Follow-Up of the CladStop Cohort.", "type": "peer-reviewed", "updated_at": "2026-11-04T12:21:22Z", "url": "https://research.draconitic.com/paper/44kds0caj4axt", "venue": "European journal of neurology", "versions": [] }