Stability in Cognition and Employment in People with Relapsing Multiple Sclerosis Treated with Cladribine Tablets: Two-year Phase IV CLARIFY-MS Study

Neurol Ther https://doi.org/10.1007/s40120-026-00897-0 ORIGINAL RESEARCH Stability in Cognition and Employment in People with Relapsing Multiple Sclerosis Treated with Cladribine Tablets: Two‑year Phase IV CLARIFY‑MS Study Bruno Brochet · Dawn Langdon · Eva Kubala Havrdova · Jeanette Lechner‑Scott Francesco Patti · Fredrik Piehl · Alessandra Solari · Raymond Hupperts Annette Lehn · Andrzej Smyk · Krzysztof Selmaj · CLARIFY-MS Investigators · Xavier Montalban · Nektaria Alexandri · · Received: December 3, 2025 / Accepted: January 29, 2026 © The Author(s) 2026, modified publication 2026 ABSTRACT Introduction: Cognitive impairment can affect people with multiple sclerosis (MS) at all stages, negatively impacting their work performance and quality of life. This study aimed to report Prior Presentation: Some results of this post hoc analysis were presented as abstracts and posters (poster numbers P089 and P090) at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, 23–25 February 2023, San Diego, California, USA. Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s40120-026-00897-0. the cognitive function and employment status data for participants with highly active relapsing MS (RMS) treated with cladribine tablets (CladT) during the 2-year, prospective, open-label, exploratory, single-arm, multicentre, phase IV CLARIFY-MS study. Methods: In this post hoc analysis, changes in cognitive function at month (M)12 and M24 (vs baseline) were measured using the Brief Interna‑ tional Cognitive Assessment for MS (BICAMS) battery. Additional analyses were conducted to assess clinically meaningful 4- and 8-point changes in Symbol Digit Modalities Test (SDMT) scores. The employment status of participants B. Brochet (*) INSERM U1215, University of Bordeaux, Bordeaux, France e-mail: X. Montalban Department of Neurology‑Neuroimmunology Centre of Multiple Sclerosis of Catalonia (Cemcat), University Hospital Vall d’Hebron, Barcelona, Spain D. Langdon Department of Psychology, Royal Holloway, University of London, Egham, Surrey, UK F. Patti Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, University of Catania, and Azienda Ospedaliero Universitaria Policlinico “G Rodolico”- San Marco, University of Catania, Catania, Italy E. K. Havrdova First Medical Faculty, Department of Neurology and Center for Clinical Neuroscience, Charles University, Prague, Czech Republic J. Lechner‑Scott University of Newcastle, Newcastle, NSW, Australia J. Lechner‑Scott Division of Neurology, John Hunter Hospital, Newcastle, NSW, Australia F. Piehl Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden A. Solari Unit of Neuroepidemiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy Vol.:(0123456789) Neurol Ther was determined through a survey at baseline and M24. Results: BICAMS parameter scores remained stable over 2 years in CladT-treated participants. As determined by a 4- and 8-point change, a high proportion of participants had increased or stable SDMT scores at M24 versus baseline. The mean annualised percentage brain volume change (PBVC) in participants was low. No cor‑ relation was found between changes in BICAMS parameter scores and annualised PBVC. Further‑ more, no major differences in the employment status of participants were observed over 2 years, with > 40% of participants being in full-time employment during the study. Conclusions: Most CLARIFY-MS participants had increased or stable information processing speed at M24 (vs baseline), as determined using clinically meaningful 4- and 8-point changes in SDMT scores. Overall, the cognitive function and employment status of CladT-treated partici‑ pants with highly active RMS remained stable over 2 years. Trial Registry Details: URL: https://clinicaltr ials.gov/ct2/show/NCT03369665; ClinicalTrials. gov Identifier: NCT03369665. PLAIN LANGUAGE SUMMARY Multiple sclerosis (MS) is an autoimmune condi‑ tion where the immune system (the body’s natu‑ ral defence system) mistakenly attacks myelin, a protective layer found around the nerve cells in the brain and spinal cord. These attacks may contribute to cognitive decline, which impacts the ability of people with MS to think, learn, and remember, causing problems in daily life and work. Cognitive decline often appears as slower information processing speed and diffi‑ culties with memory and verbal fluency. Clad‑ ribine tablets are an oral medication for treat‑ ing relapsing forms of MS, taken in two short courses over two consecutive years. Each treat‑ ment course consists of two treatment weeks, one at the beginning of the first month and one at the beginning of the second month. Relapses are periods where new MS symptoms appear or existing symptoms worsen over 24 h or longer. In the CLARIFY-MS study, researchers studied the changes in cognitive function and employ‑ ment status over 2 years in people with highly active relapsing MS treated with cladribine tab‑ lets. The majority of participants in CLARIFY-MS showed increased or stable information process‑ ing speed at 24 months compared to the start of the study. Overall, cognitive function, including verbal learning and visual memory, remained stable over 2 years. Most participants who were employed full-time at the start of the study retained their employment status even after 2 years. The stability in cognitive function and employment status observed during CLARIFYMS supports previously reported positive qual‑ ity-of-life findings in people with highly active relapsing MS treated with cladribine tablets. Keywords: BICAMS; Cladribine tablets; CLARIFY-MS; Cognition; Employment; Multiple Sclerosis; MS; Relapsing MS; SDMT; Work Key Summary Points Why carry out this study? R. Hupperts Zuyderland Medisch Centrum Sittard, Maastricht University Medical Center, Maastricht, The Netherlands N. Alexandri · A. Lehn · A. Smyk Merck Healthcare KGaA, Darmstadt, Germany K. Selmaj Center for Neurology, Lodz, Poland K. Selmaj Department of Neurology, University of Warmia and Mazury, Olsztyn, Poland Cognitive impairment can affect people with multiple sclerosis (MS) at all stages, nega‑ tively impacting their work performance and overall quality of life. Cladribine tablets (CladT; 3.5 mg/kg cumu‑ lative dose over 2 years) are a high-efficacy therapy indicated for the treatment of relaps‑ ing MS (RMS). Neurol Ther This study aimed to report cognitive func‑ tion and employment data from people with highly active RMS treated with CladT during the 2-year phase IV CLARIFY-MS study. What was learned from the study? Most CLARIFY-MS participants had increased or stable information processing speed at 24 months (vs baseline), as determined using clinically meaningful 4- and 8-point changes in Symbol Digit Modalities Test (SDMT) scores. Overall cognitive function, includi (...truncated)