Circulating microRNA as biomarkers for predicting cladribine response in multiple sclerosis

Reliable biomarkers capturing early biological responses to treatment in multiple sclerosis (MS) remain limited. Circulating microRNAs (miRNAs) may provide complementary information on treatment-related biological changes and subsequent clinical response. We prospectively evaluated circulating miRNAs in 20 patients with relapsing-remitting MS initiating cladribine tablets.

Twenty-one miRNAs were measured at baseline and approximately six months after treatment initiation, with clinical outcomes assessed over 24 months. Seven miRNAs showed significant treatment-associated changes after Benjamini-Hochberg correction. A fixed three-miRNA model discriminated baseline from post-treatment samples with an apparent AUC of 0.79 (95% CI, 0.67–0.91) and a leave-one-pair-out cross-validated AUC of 0.78 (95% CI, 0.64–0.90).

Separately, on-treatment miR-320 family levels, which did not show significant treatment-associated changes, were associated with subsequent NEDA-3, with AUCs up to 0.84 (95% CI, 0.64–1.00), suggesting a potential role in early response assessment. In patients with available neurofilament light chain measurements, there was no significant difference in predictive performance between hsa-miR-320b and neurofilament light chain. These findings suggest that circulating miRNAs may capture distinct aspects of biological treatment effects and subsequent clinical response to cladribine and warrant further investigation as complementary biomarkers for treatment monitoring and response assessment in larger independent cohorts.

This study was supported by Merck Ltd. The sponsor had no role in the study design, data collection, data analysis, interpretation of the results, or the writing of the manuscript. The author declared that financial support was received for the research.

Merck Serono Ltd., Herzliya, Israel, an affiliate of Merck KGaA, Darmstadt, Germany sponsored the study. Gray Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel Neuroimmunology and Multiple Sclerosis Unit, Neurology Institute, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv, 6423906, Israel Ifat Vigiser, Hadar Kolb, Maya Golan, Arnon Karni & Keren Regev Research Department, Levinsky-Wingate Academic Center, Netanya, Israel Department of Neurology, Assuta Medical Center, Tel Aviv, Israel Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel Department of Neurology, Mayo Clinic in Florida, Jacksonville, FL, USA The authors declare no competing interests. The study was approved by the Institutional Review Board of Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (approval number 0194-13-TLV), and was conducted in accordance with the principles of the Declaration of Helsinki.

Written informed consent was obtained from all participants prior to inclusion in the study. Ifat Vigiser has received research support from Biogen and Merck-Serono. Keren Regev has received research support from Biogen and Merck-Serono.