Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Ann Clin Transl Neurol. 2024 Sep;11(9):2485-2498. doi: 10.1002/acn3.52167. Epub 2024 Aug 26.
Circulating metabolite levels are altered in multiple sclerosis (MS) and are associated with MS severity. However, how metabolic profiles shift following highly efficacious therapies, like ocrelizumab remains unclear.
Circulating metabolite levels are altered in multiple sclerosis (MS) and are associated with MS severity. However, how metabolic profiles shift following highly efficacious therapies, like ocrelizumab remains unclear. To assess changes in the circulating metabolome produced by ocrelizumab treatment in people with relapsing-remitting MS (RRMS).
Thirty-one individuals with RRMS eligible for beginning treatment with ocrelizumab were recruited and followed with demographic, clinical, quality-of-life, and global metabolomics data collected at each visit. Modules of highly correlated metabolites were identified using the weighted correlation network analysis approach. Changes in each module's eigenmetabolite values and individual metabolites during the study were evaluated using linear mixed-effects models.
Patients with a mean age of 40.8 (SD = 10.30) years, and median disease duration of 4.0 (IQR = 8.5) years, were monitored for a median of 3.36 (IQR = 1.43) years. Two out of twelve identified sets of metabolites were altered significantly. The first module mainly contained androgenic and pregnenolone steroids (p-value <0.001, coefficient: -0.10). The second module primarily consisted of several lysophospholipids, arachidonic acid, some endocannabinoids, and monohydroxy fatty acid metabolites (p-value = 0.016, coefficient: -0.12), which its reduction was significantly associated with improvement based on overall disability response score (OR 3.09e-01, 95% CI: 6.83e-02, 9.09e-01, p-value = 3.15E-02).
In this longitudinal observational study, using a global untargeted metabolomics approach, we showed significant alteration in circulating metabolome in RRMS patients undergoing ocrelizumab treatment. In particular, we observed a significant reduction in metabolites involved in the lysophospholipid pathway, which was associated with patients' improvement.
多发性硬化症（MS）患者的循环代谢物水平发生改变，且与 MS 严重程度相关。然而，奥瑞珠单抗等高效疗法治疗后，代谢谱如何变化尚不清楚。
多发性硬化症（MS）患者的循环代谢物水平发生改变，且与 MS 严重程度相关。然而，奥瑞珠单抗等高效疗法治疗后，代谢谱如何变化尚不清楚。本研究旨在评估奥瑞珠单抗治疗对复发缓解型多发性硬化症（RRMS）患者的循环代谢组学的影响。
招募了 31 名符合奥瑞珠单抗治疗条件的 RRMS 患者，并在每次就诊时收集人口统计学、临床、生活质量和全局代谢组学数据。采用加权相关网络分析方法鉴定高度相关代谢物模块。使用线性混合效应模型评估研究期间每个模块的特征代谢物值和单个代谢物的变化。
患者平均年龄为 40.8 岁（标准差=10.30），中位疾病持续时间为 4.0 年（IQR=8.5），中位监测时间为 3.36 年（IQR=1.43）。鉴定出的十二组代谢物中有两组发生显著改变。第一个模块主要包含雄激素和孕烯醇酮类固醇（p 值<0.001，系数：-0.10）。第二个模块主要由几种溶血磷脂、花生四烯酸、一些内源性大麻素和单羟基脂肪酸代谢物组成（p 值=0.016，系数：-0.12），其降低与根据总体残疾反应评分得出的改善显著相关（OR 3.09e-01，95%CI：6.83e-02，9.09e-01，p 值=3.15E-02）。
在这项纵向观察性研究中，我们使用全局非靶向代谢组学方法表明，接受奥瑞珠单抗治疗的 RRMS 患者的循环代谢组发生了显著改变。特别是，我们观察到参与溶血磷脂途径的代谢物显著减少，这与患者的改善相关。
