Work

A two year clinical, immunological and gut-brain-axis prospective study to predict treatment response to cladribine tablets in relapsing-remitting multiple sclerosis

Year: 2026

Type: article

Abstract: Introduction In relapsing-remitting multiple sclerosis (RRMS) it is challenging to predict which person will benefit from a certain therapy, such as cladribine tablets (CladT). This study aimed to obtain a better understanding of the interaction between the gut-brain axis and CladT to improve treatment response prediction. Methods In this multicenter, prospective, observational study, we included 81 people with RRMS starting CladT. We assessed the clinical, immunological and microbiological profiles at baseline and after 3, 12 and 24 months, and compared results between responders and non-responders, classified based on inflammatory disease activity and disability progression (NEDA-3). Results A total of 35 of 81 (47%) participants were responders. We found no differences in immune cell profiles between responders and non-responders. Network analysis revealed more positive correlations between immune cell clusters within the same parent cluster and a stronger negative correlation between CD8 + T cells and myeloid cells in responders. Microbiological analyses showed that fecal alpha diversity, both overall and for Bacteroidetes, as well as the relative abundance of the species Bacteroides caccae and Prevotella copri in fecal samples, are associated with treatment response to CladT. Discussion Although we found a trend toward more coordinated immune reorganization in CladT responders, and identified fecal alpha diversity and fecal Bacteroides caccae and Prevotella copri as associated with treatment response, we could not develop a reliable model to predict treatment response before or shortly after the start of CladT. Our results warrant further investigation in larger cohorts.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1955097