Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Eur J Neurol. 2023 Jan;30(1):187-194. doi: 10.1111/ene.15588. Epub 2022 Oct 25.
In a recent trial, hydroxychloroquine (HCQ) treatment reduced the expected rate of disability worsening at 18 months in primary progressive multiple sclerosis (PPMS). Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are emerging biomarkers in multiple sclerosis.
We measured NfL and GFAP levels in serum samples from 39 patients with inactive PPMS included in a phase II clinical trial of HCQ treatment in PPMS at multiple time points over 18 months, and investigated the association of these biomarkers with clinical disability at screening and during follow-up. Screening and 12-month retinal nerve fiber layer (RNFL) thickness was also recorded and analyzed.
NfL and GFAP levels increased over time, but only significantly from screening to month 6. NfL and GFAP levels did not significantly increase from month 6 up to month 18. At screening, NfL and GFAP levels did not correlate with the Expanded Disability Status Scale (EDSS), and GFAP but not NfL modestly correlated with Timed 25-Foot Walk test (T25FW). Screening NfL and GFAP levels did not predict disability worsening (≥20% worsening on the T25FW) at month 18. RNFL thickness decreased significantly from screening to month 12 and independently predicted disability worsening.
In this cohort of people with inactive PPMS, HCQ treatment attenuated the increase of NfL and GFAP after 6 months of treatment and up to 18 months of follow-up, suggesting a treatment effect of HCQ over these biomarkers. RNFL thickness, a marker of neuroaxonal atrophy, was associated with disability worsening, and should be explored further as a prognostic marker in this population.
在最近的一项试验中，羟氯喹（HCQ）治疗降低了原发性进展型多发性硬化症（PPMS）患者在 18 个月时残疾恶化的预期发生率。神经丝轻链（NfL）和胶质纤维酸性蛋白（GFAP）是多发性硬化症的新兴生物标志物。
我们在一项 HCQ 治疗 PPMS 的 II 期临床试验中，对 39 例处于静止期 PPMS 患者的血清样本进行了 NfL 和 GFAP 水平的测量，这些患者在 18 个月的时间内进行了多次检测，并对这些生物标志物与筛查和随访期间的临床残疾进行了相关性研究。同时还记录和分析了筛查和 12 个月时视网膜神经纤维层（RNFL）厚度。
NfL 和 GFAP 水平随时间增加，但仅在筛查至 6 个月时显著增加。从第 6 个月到第 18 个月，NfL 和 GFAP 水平没有显著增加。在筛查时，NfL 和 GFAP 水平与扩展残疾状态量表（EDSS）不相关，GFAP 而不是 NfL 与 Timed 25-Foot Walk test（T25FW）呈中度相关。筛查时的 NfL 和 GFAP 水平不能预测第 18 个月时的残疾恶化（T25FW 恶化≥20%）。从筛查到第 12 个月，RNFL 厚度显著下降，并独立预测残疾恶化。
在这组处于静止期的 PPMS 患者中，HCQ 治疗在治疗 6 个月后和随访 18 个月内，减弱了 NfL 和 GFAP 的增加，表明 HCQ 对这些生物标志物有治疗作用。RNFL 厚度是神经轴突萎缩的标志物，与残疾恶化相关，应该作为该人群的预后标志物进一步探讨。
