Stability in Cognition and Employment in People with Relapsing Multiple Sclerosis Treated with Cladribine Tablets: Two-year Phase IV CLARIFY-MS Study
Neurol Ther. 2026-03-10; :
DOI: 10.1007/s40120-026-00897-0
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https://www.bordeaux-neurocampus.fr/12527
Brochet B(1), Langdon D(2), Havrdova EK(3), Lechner-Scott J(4)(5), Montalban X(6), Patti F(7), Piehl F(8), Solari A(9), Hupperts R(10), Alexandri N(11), Lehn A(11), Smyk A(11), Selmaj K(12)(13); CLARIFY-MS Investigators.
Author information:
(1)INSERM U1215, University of Bordeaux, Bordeaux, France.
.
(2)Department of Psychology, Royal Holloway, University of London, Egham,
Surrey, UK.
(3)First Medical Faculty, Department of Neurology and Center for Clinical
Neuroscience, Charles University, Prague, Czech Republic.
(4)University of Newcastle, Newcastle, NSW, Australia.
(5)Division of Neurology, John Hunter Hospital, Newcastle, NSW, Australia.
(6)Department of Neurology-Neuroimmunology Centre of Multiple Sclerosis of
Catalonia (Cemcat), University Hospital Vall d’Hebron, Barcelona, Spain.
(7)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.
(8)Department of Clinical Neuroscience, Karolinska Institutet, Stockholm,
Sweden.
(9)Unit of Neuroepidemiology, Fondazione IRCCS Istituto Neurologico Carlo Besta,
Milan, Italy.
(10)Zuyderland Medisch Centrum Sittard, Maastricht University Medical Center,
Maastricht, The Netherlands.
(11)Merck Healthcare KGaA, Darmstadt, Germany.
(12)Center for Neurology, Lodz, Poland.
(13)Department of Neurology, University of Warmia and Mazury, Olsztyn, Poland.
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 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 International 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 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 correlation was found between changes in BICAMS parameter scores and
annualised PBVC. Furthermore, 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 participants with highly active RMS remained
stable over 2 years.
TRIAL REGISTRY DETAILS: URL: https://clinicaltrials.gov/ct2/show/NCT03369665 ;
ClinicalTrials.gov Identifier: NCT03369665.
Plain Language Summary: Multiple sclerosis (MS) is an autoimmune condition where
the immune system (the body’s natural 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
difficulties with memory and verbal fluency. Cladribine tablets are an oral
medication for treating relapsing forms of MS, taken in two short courses over
two consecutive years. Each treatment 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 employment status over 2 years in people with
highly active relapsing MS treated with cladribine tablets. The majority of
participants in CLARIFY-MS showed increased or stable information processing
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 CLARIFY-MS supports previously
reported positive quality-of-life findings in people with highly active
relapsing MS treated with cladribine tablets.
© 2026. The Author(s).
DOI: 10.1007/s40120-026-00897-0
PMID: 41806309
Conflict of interest statement: Declarations. Conflict of Interest: The authors
declare the following potential conflicts of interest: Bruno Brochet has
received consultancy fees and speaker fees from Merck and Sanofi. Dawn Langdon
has participated in speaker bureaus for Almirall, Bayer, Biogen, Bristol Myers
Squibb (BMS), Merck, Novartis, Roche, Sanofi, and Teva; has received consultancy
fees from Bayer, Biogen, BMS, Merck, Novartis, and Teva; and has received
research grants from Bayer, Biogen, Merck, and Novartis. Dawn Langdon is an
Editorial Board member of Neurology and Therapy, and was not involved in the
selection of peer reviewers for the manuscript nor any of the subsequent
editorial decisions. Eva Kubala Havrdova received financial support for
conference travel, and/or speaker honoraria, and/or research support, and/or
consultant fees from Actelion, Biogen, Celgene, Merck, Novartis, Roche, Sanofi,
and Teva. She has been supported by the Czech Ministry of Education—project
Cooperatio LF1, research area Neuroscience—and by the General University
Hospital in Prague project MH CZ-DRO-VFN64165. Jeanette Lechner-Scott has
received travel compensation from Biogen, Merck, and Novartis. Her institution
receives honoraria for talks and advisory board commitments as well as research
grants from Biogen, Merck, Novartis, and Roche. Xavier Montalban’s institution
has received compensation for lecture honoraria and travel expenses,
participation in scientific meetings, clinical trial steering committee
membership, or clinical advisory board participation in recent years from
AbbVie, Actelion, Alexion, AstraZeneca, Autolus, Bial PD, Biogen, BMS/Celgene,
Genzyme, Hoffmann-La Roche, Immunic Therapeutics, Indivi, Janssen
Pharmaceuticals, Juvisé Pharmaceutical, Lilly, MedDay, Medscape, Merck,
Mylan-Viatris, Nervgen, Neuraxpharm, Novartis, PeerVoice, Rewind Therapeutics,
Samsung-Biosys, Sandoz, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics,
Zenas Biopharma, Excemed, ECTRIMS, MSIF, and NMSS, or any of their affiliates.
Francesco Patti has received personal compensation for speaking activities or
serving on advisory boards from Alexion, Almirall, Biogen, BMS, Johnson &
Johnson, Merck, Novartis, Roche, and Sanofi. He has also received research
grants from Alexion, Almirall, the Italian Ministry of Health, Merck, MIUR,
Novartis, Roche, and Sanofi. He is Associate Editor of Frontiers in Neurology.
Francesco Patti is an Editorial Board member of Neurology and Therapy. He was
not involved in the selection of peer reviewers for the manuscript nor any of
the subsequent editorial decisions. Fredrik Piehl has received research grants
from Janssen, Merck, and Sanofi; fees for serving as a member of the DMC in
clinical trials with Lundbeck, Parexel, and Roche; and fees for the preparation
of witness statements for Novartis. Alessandra Solari has served on advisory
boards for Almirall and Merck and has been invited to speak on behalf of the
same companies. She has also received research grants from the Italian MS
Society. Raymond Hupperts has received institutional research grants and fees
for lectures and advisory boards from Biogen, Merck, and Sanofi. Nektaria
Alexandri, Annette Lehn, and Andrzej Smyk are employees of Merck Healthcare
KGaA, Darmstadt, Germany. Krzysztof Selmaj has received honoraria for speaking,
consulting, and serving on advisory boards for Biogen, Celgene (BMS), Merck,
Novartis, Roche, and TG Therapeutics. Ethical Approval: The CLARIFY-MS study was
conducted in accordance with the principles outlined in the Declaration of
Helsinki and the International Council for Harmonisation Guidelines for Good
Clinical Practice. This study was approved by independent ethics committees or
institutional review boards at each study site. Participants provided written
informed consent prior to the initiation of any study-related activities.
Details of all institutional review boards and ethics committees are available
in Supplementary Table S5.