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

@article{pamelen2026year,
  title = {{A two year clinical, immunological and gut-brain-axis prospective study to predict treatment response to cladribine tablets in relapsing-remitting multiple sclerosis}},
  author = {Jeske van Pamelen and Chaja M. J. van Ansenwoude and Maria Miguélez Sánchez and Lotte Spijkerbosch and Carla Rodriguez-Mogeda and Lynn van Olst and Susanne M. A. van der Pol and Maarten L. Boon and Marleen J. A. Koel-Simmelink and Tom van Seeters and Birgit I. Lissenberg-Witte and Janet de Beukelaar and Jiske Fermont and Stephan T. F. M. Frequin and Oliver H. H. Gerlach and Guy Laureys and Bob W. van Oosten and Judith van Vliet and Joep Killestein and Charlotte E. Teunissen and Andries E. Budding and Helga E. de Vries and Leo H. Visser},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1955097},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1955097/full},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - A two year clinical, immunological and gut-brain-axis prospective study to predict treatment response to cladribine tablets in relapsing-remitting multiple sclerosis
AU  - Jeske van Pamelen
AU  - Chaja M. J. van Ansenwoude
AU  - Maria Miguélez Sánchez
AU  - Lotte Spijkerbosch
AU  - Carla Rodriguez-Mogeda
AU  - Lynn van Olst
AU  - Susanne M. A. van der Pol
AU  - Maarten L. Boon
AU  - Marleen J. A. Koel-Simmelink
AU  - Tom van Seeters
AU  - Birgit I. Lissenberg-Witte
AU  - Janet de Beukelaar
AU  - Jiske Fermont
AU  - Stephan T. F. M. Frequin
AU  - Oliver H. H. Gerlach
AU  - Guy Laureys
AU  - Bob W. van Oosten
AU  - Judith van Vliet
AU  - Joep Killestein
AU  - Charlotte E. Teunissen
AU  - Andries E. Budding
AU  - Helga E. de Vries
AU  - Leo H. Visser
PY  - 2026
DA  - 2026/10/19
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1955097
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1955097/full
AB  - 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.
SN  - 1664-3224
ER  -