Long-term follow-up of patients with a first clinical demyelinating event (clinically isolated syndrome) who received cladribine tablets in CLASSIC-MS: Findings for the ORACLE-MS cohort

Gavin Giovannoni; Alexey Boyko; Jorge Correale; Gilles Edan; Mark S Freedman; Xavier Montalban; Kottil Rammohan; Dusan Stefoski; Bassem Yamout; Thomas Leist; Aida Aydemir; Laszlo Borsi; Elisabetta Verdun di Cantogno

doi:10.1177/13524585241302170

Long-term follow-up of patients with a first clinical demyelinating event (clinically isolated syndrome) who received cladribine tablets in CLASSIC-MS: Findings for the ORACLE-MS cohort

Mult Scler. 2024 Dec 17:13524585241302170. doi: 10.1177/13524585241302170. Online ahead of print.

Authors

Affiliations

¹ Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.
² Department of Neurology, Pirogov Russian National Research Medical University, Neurosurgery and Medical Genetics, Federal Center of Brain Research and Neurotechnologies, Moscow, Russia.
³ Department of Neurology, FLENI Institute, Buenos Aires, Argentina.
⁴ Department of Neurology, University Hospital of Rennes, Rennes, France.
⁵ Department of Medicine and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada.
⁶ Department of Neurology, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitario Vall d'Hebron, Barcelona, Spain.
⁷ University of Miami School of Medicine, MS Research Center, Miami, FL, USA.
⁸ Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
⁹ Neurology Institute, Harley Street Medical Center, Abu Dhabi, UAE; American University of Beirut Medical Center, Beirut, Lebanon.
¹⁰ Division of Clinical Neuroimmunology, Jefferson University, Comprehensive MS Center, Philadelphia, PA, USA.
¹¹ EMD Serono Research & Development Institute, Inc., an affiliate of Merck KGaA, Billerica, MA, USA.
¹² Merck Healthcare KGaA, Darmstadt, Germany.

PMID: 39690897
DOI: 10.1177/13524585241302170

Abstract

Background: CLASSIC-MS explored long-term outcomes of patients treated with cladribine tablets.

Objective: Assess long-term efficacy in patients previously enrolled in ORACLE-MS, a Phase III parent trial.

Methods: ORACLE-MS included patients with a first clinical demyelinating event (FCDE or clinically isolated syndrome) who received ⩾1 course of cladribine tablets or placebo. With a median follow-up time of 9.5 years, CLASSIC-MS assessed conversion rates to clinically definite multiple sclerosis (CDMS), time-to-conversion, relapse rates, long-term mobility/disability status and subsequent disease-modifying therapy (DMT) use.

Results: Of 227 patients from the ORACLE-MS cohort of 616, 68.7% were exposed to cladribine tablets and 31.3% were never exposed. Of the exposed patients at risk, 51.5% converted to CDMS with a median conversion time of 8.4 (95% confidence interval (CI): 5.4-not estimable) years, versus 80.6%, median time 0.8 (95% CI: 0.3-2.4) years, for never exposed. Exposed patients were less likely to be using a wheelchair or ambulatory device or receive subsequent DMTs, and 53.2% were relapse-free versus 28.2% never exposed.

Conclusions: Proportionally, more FCDE patients exposed to cladribine tablets experienced delayed conversion to CDMS and fewer relapses and were less likely to use a wheelchair or ambulatory device than never-exposed patients, at 9.5 years (median).

Keywords: Cladribine tablets; Expanded Disability Status Scale; disability; disease-modifying therapy; first clinical demyelinating event; multiple sclerosis.