Department of Neurology, University Hospital of Strasbourg, Strasbourg, France.
Neurological Clinic and Polyclinic, Departments of Medicine, Clinical Research and Biomedical Engineering, University Hospital Basel, University of Basel, Basel, Switzerland.
Brain Behav. 2021 Feb;11(2):e01998. doi: 10.1002/brb3.1998. Epub 2020 Dec 13.
High-dose pharmaceutical-grade biotin (MD1003) has positive effects on disability in progressive multiple sclerosis (PMS), but its mechanism of action remains unclear. The objective of our study was to quantify the effect of MD1003 in patients with PMS, using clinical response, plasma neurofilament light chain (pNfL) levels, and brain (BV) or cervical spinal cord volume (CSCV).
Forty-eight patients with PMS newly treated with MD1003 were followed during one year. Patients were assessed clinically using the Expanded Disability Status Scale (EDSS), the nine-hole peg test (9HPT), and the 25-foot walk time (25FWT). CSCV was quantified using CORDIAL software and BV using SIENA or SIENAX. We measured pNfL level using SIMOA at several time points. Bayesian linear and logistic regressions were used to evaluate potential prognostic factors.
Treatment response, defined as a significant decrease of EDSS, 25FWT, or 9HPT at 1 year, was observed in 13 patients (27%). A gain of volume was noted in 7/24 patients for brain and in 10/19 patients for cervical spinal cord. The strongest predictors of poor treatment response were a high pNfL level at MD1003 onset (OR 0.96; 95% CI [0.91; 1]), high age at MS onset (OR 0.95; 95% CI [0.89; 1.01]), and an increase in brain lesion load during MD1003 treatment (OR 0.81; 95% CI [0.55; 1.05]).
MD1003 treatment was associated with clinical, BV, and CSCV improvement at 1 year. The correlation between the levels of pNfL at baseline, the age at multiple sclerosis onset, and a treatment response at M12 is consistent with a better effect in less disabled patients.
高剂量医药级生物素（MD1003）对进展型多发性硬化症（PMS）的残疾有积极影响，但作用机制尚不清楚。我们的研究目的是通过临床反应、血浆神经丝轻链（pNfL）水平和脑（BV）或颈脊髓体积（CSCV）来量化 MD1003 对 PMS 患者的治疗效果。
48 例新接受 MD1003 治疗的 PMS 患者在一年的时间里接受了随访。患者通过扩展残疾状况量表（EDSS）、九孔钉测试（9HPT）和 25 英尺步行时间（25FWT）进行临床评估。使用 CORDIAL 软件对 CSCV 进行量化，使用 SIENA 或 SIENAX 对 BV 进行量化。我们使用 SIMOA 在多个时间点测量 pNfL 水平。贝叶斯线性和逻辑回归用于评估潜在的预后因素。
13 例患者（27%）在 1 年内出现 EDSS、25FWT 或 9HPT 显著下降的治疗反应。24 例患者中有 7 例脑体积增加，19 例患者中有 10 例颈脊髓体积增加。治疗反应不良的最强预测因素是 MD1003 发病时 pNfL 水平较高（OR 0.96；95%CI [0.91；1]）、多发性硬化症发病时年龄较高（OR 0.95；95%CI [0.89；1.01]）和 MD1003 治疗期间脑病变负荷增加（OR 0.81；95%CI [0.55；1.05]）。
MD1003 治疗与 1 年后的临床、BV 和 CSCV 改善相关。基线时 pNfL 水平、多发性硬化症发病年龄与 M12 时治疗反应之间的相关性与在残疾程度较低的患者中效果更好一致。
