van Pamelen Jeske, Rodriguez-Mogeda Carla, van Olst Lynn, van der Pol Susanne M A, Boon Maarten L, de Beukelaar Janet, Gerlach Oliver H H, Budding Andries E, Killestein Joep, de Vries Helga E, Visser Leo H
Department of Neurology, Elisabeth-TweeSteden Hospital, Tilburg, Netherlands.
Multiple Sclerosis (MS) Center Amsterdam, Amsterdam Neuroscience, Amsterdam University Medical Center (UMC) Location Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Front Immunol. 2025 Feb 27;16:1514762. doi: 10.3389/fimmu.2025.1514762. eCollection 2025.
Cladribine tablets are an effective treatment for relapsing remitting multiple sclerosis (RRMS). However, almost half of the treated patients are not free of disease activity after two years. The aim of this study was to describe the changes that cladribine tablets effectuate in the gut and oral microbiota and the peripheral immunological profile between responders and non-responders.
In this pilot study of the multicenter, prospective, observational BIA (Brain-Immune-Intestine Axis) study, we included patients aged 18 to 55 years with RRMS who were scheduled to start treatment with cladribine tablets. We assessed the clinical status and the immunological and microbiological profile prior to the start of the treatment and after three and twelve months. At twelve months, we assessed the response status, based on clinical relapses, radiological activity and disability progression on the Expanded Disability Status Scale.
The first twenty-five patients of the BIA study were included in this analysis. Ten patients (40%) were responders twelve months after treatment. Three months after treatment we found a significant decline of naïve and transitional B cells and memory B cells, and of CD57 CD56 NK cells. After twelve months the values recovered to baseline levels, except for the memory B cells. We did not find significant changes of the microbiological profile over time, except for a decline of the phylum in the oral samples twelve months after treatment. Baseline values and changes over time did not significantly differ between responders and non-responders. However, several phyla, genera or species ( showed a higher relative abundance, and several phyla, genera or species ( had a lower relative abundance in responders compared to non-responders.
After treatment with cladribine tablets, we found significant changes in the immunological landscape. Also, the microbiological profile showed several differences in microbes with known anti- or pro-inflammatory properties between responders and non-responders. Overall, we showed that we can measure a treatment effect from cladribine tablets with our analyses. Future research on data from the BIA study, with a larger sample size and extended follow-up, can possibly confirm the reliability of our findings.
克拉屈滨片是复发缓解型多发性硬化症（RRMS）的一种有效治疗方法。然而，几乎一半接受治疗的患者在两年后仍有疾病活动。本研究的目的是描述克拉屈滨片对肠道和口腔微生物群以及应答者和非应答者外周免疫谱的影响。
在这项多中心、前瞻性、观察性脑-免疫-肠轴（BIA）研究的初步研究中，我们纳入了年龄在18至55岁之间、计划开始使用克拉屈滨片治疗的RRMS患者。我们在治疗开始前以及治疗三个月和十二个月后评估了临床状况、免疫和微生物谱。在十二个月时，我们根据临床复发、影像学活动以及扩展残疾状态量表上的残疾进展评估了应答状态。
BIA研究的前25名患者被纳入本分析。10名患者（40%）在治疗十二个月后为应答者。治疗三个月后，我们发现初始B细胞、过渡性B细胞、记忆B细胞以及CD57 CD56自然杀伤细胞显著减少。十二个月后，除记忆B细胞外，这些值恢复到基线水平。除治疗十二个月后口腔样本中某一门的细菌减少外，我们未发现微生物谱随时间有显著变化。应答者和非应答者之间的基线值和随时间的变化无显著差异。然而，与非应答者相比，应答者中有几个门、属或种的相对丰度较高，有几个门、属或种的相对丰度较低。
使用克拉屈滨片治疗后，我们发现免疫格局有显著变化。此外，微生物谱显示应答者和非应答者之间在具有已知抗炎或促炎特性的微生物方面存在一些差异。总体而言，我们表明通过我们的分析可以测量克拉屈滨片的治疗效果。未来对BIA研究数据进行的样本量更大、随访时间更长的研究可能会证实我们研究结果的可靠性。
