Blood Biomarker Dynamics in People with Relapsing Multiple Sclerosis Treated with Cladribine Tablets: Results of the 2-Year MAGNIFY-MS Study

Multiple sclerosis (MS) is a chronic immune-mediated disease that affects the central nervous system. Most approved disease modifying therapies require continuous administration and act by suppressing the immune system to deliver beneficial effects. Cladribine tablets represent an effective immune reconstitution therapy for the treatment of relapsing MS and are administered in short treatment courses over two consecutive years.

To better understand the amplitude of immune changes following cladribine tablets treatment, we performed a comprehensive immune-phenotyping analysis during the 2-year study period of MAGNIFY-MS (NCT03364036). This animated video presents the findings of this analysis.

Over the 24-month study period, reductions were found in most B, T, and natural killer (NK) cells at month 3 after initiating treatment with cladribine tablets. Naïve, transitional, and regulatory B cells repopulated to above baseline levels by months 12 and 24, and NK cell subtypes CD16^lowCD56^bright and NKp46 cells reconstituted at month 6 and month 12, respectively. All other B, T and NK cell subsets remained below baseline levels by the end of the study. Reductions in pro-inflammatory cytokine-producing B and T cells and increases in anti-inflammatory cytokine-producing T cells were also observed. Altogether, cladribine tablets were found to rebalance the immune system towards a more homeostatic and less pathogenic state, distinguishing the treatment from other high-efficacy disease-modifying therapies and continuous immunosuppression approaches.

Original Article:

Wiendl H, Barkhof F, Montalban X, et al. Blood biomarker dynamics in people with relapsing multiple sclerosis treated with cladribine tablets: results of the 2-year MAGNIFY-MS study. Front Immunol. 2025;16:1512189. DOI: 10.3389/fimmu.2025.1512189

Meet the Lead Author:

Heinz Wiendl studied medicine in Germany, Switzerland, and the USA, graduating in 1996. After working as a research fellow at the Institute of Neuroanatomy, Nuremberg, and the Max Planck Institute for Neurobiology and the Department of Neurology, Tuebingen, he became head of the clinical research group for multiple sclerosis (MS) in Wuerzburg in 2005 and acted as a vice-chair of the Department of Neurology. In 2010, he was recruited to the University Hospital Muenster as director of the Department of Neurology – Inflammatory Disorders of the Nervous System and Neurooncology. From May 2013 until September 2024, Prof. Wiendl served as head of the Department of Neurology, Muenster – to which the Institute of Translational Neurology has been associated since 2018. Prof. Wiendl is head of the Department of Neurology and Neurophysiology in Freiburg since October 2024.

His research focuses on inflammatory neurodegeneration and immune regulation and protection as well as monitoring MS and its therapy. His achievements have been recognized by both Sobek awards of the German Society for MS (DMSG) (2004; 2015). In 2017, he was appointed Honorary Professor at Sydney Medical School and in 2020 he received an honorary doctorate from the Medical Faculty of Masshad/Iran.

Heinz Wiendl is a member of numerous scientific and academic advisory boards and expert panels, including editorial boards of international scientific journals in the fields of neurology, neurosciences, and immunology, as well as for societies, foundations, and project promoters. He is speaker of the disease-related competence network Multiple Sclerosis (KKNMS) and the founder and principal investigator of the “Body and Brain Institute” Muenster, a prestigious research building funded by the German Federal Ministry.