MicroRNA Expression Profiles as Biomarkers of Response to Disease-Modifying Therapies in Multiple Sclerosis: A...

Although microRNAs (miRNAs) are an active area of research in multiple sclerosis (MS) and have been proposed as potential biomarkers of treatment response, the evidence remains difficult to interpret. This systematic review examines the relationship between miRNA expression and response to disease-modifying therapies (DMTs) in adults with MS. The PubMed/MEDLINE and Web of Science databases were systematically searched from inception to 11 February 2026. Fifteen studies that compared miRNA expression between responders and non-responders or assessed changes in miRNA expression after DMT initiation were synthesized narratively by treatment group and outcome, in accordance with the 2020 PRISMA guidelines. After considering study design, treatment response definitions, and miRNA analytical methods, miR-548a-3p in fingolimod-treated patients and miR-223-3p, miR-23a/b-3p, and miR-27a/b-3p in dimethyl fumarate (DMF)-treated patients appeared the most promising miRNAs investigated; however, each was assessed in a single study and has not yet been validated in independent external cohorts. However, they were notable because they had been evaluated in clinically relevant settings: miR-548a-3p in relation to no evidence of disease activity-3 and receiver operating characteristic-based discrimination, and the DMF-associated miRNAs through baseline expression levels and early fold-change analyses. Although miR-23a-3p, miR-26a-5p, miR-146a-5p, miR-155, miR-34a-5p, miR-223-3p, miR-660-5p, and miR-326 had been reported in more than one study, most were investigated in different DMT or outcome contexts. Therefore, the existing literature correlating miRNA expression levels with treatment response provides valuable but limited and heterogeneous evidence. Thus, miRNAs should currently be considered exploratory biomarkers and require further independent validation before their use in clinical practice.