芬戈莫德对多发性硬化症患者脑灰质、丘脑和白质的影响。
Fingolimod effect on gray matter, thalamus, and white matter in patients with multiple sclerosis.
机构信息
From the Medical Image Analysis Centre (L.G., E.-W.R., N.M.-L., T.S.), University Hospital Basel; Neurologic Clinic and Policlinic (L.G., L.K., T.S.), Departments of Medicine, Clinical Research, Biomedicine, and Biomedical Engineering, University Hospital and University of Basel; Novartis Pharma AG (D.A.H., D.T.), Basel, Switzerland; Novartis Healthcare Pvt Ltd (A.T.), Hyderabad, India; and Department of Neurology (T.S.), DKD HELIOS Klinik Wiesbaden, Germany.
出版信息
Neurology. 2018 Apr 10;90(15):e1324-e1332. doi: 10.1212/WNL.0000000000005292. Epub 2018 Mar 14.
OBJECTIVE
To study the effect of fingolimod on deep gray matter (dGM), thalamus, cortical GM (cGM), white matter (WM), and ventricular volume (VV) in patients with relapsing-remitting multiple sclerosis (RRMS).
METHODS
Data were pooled from 2 phase III studies. A total of 2,064 of 2,355 (88%) contributed to the analysis: fingolimod 0.5 mg n = 783, fingolimod 1.25 mg n = 799, or placebo n = 773. Percentage change from baseline in dGM and thalamic volumes was evaluated with FMRIB's Integrated Registration & Segmentation Tool; WM, cGM, and VV were evaluated with structural image evaluation using normalization of atrophy cross-sectional version (SIENAX) at months 12 and 24.
RESULTS
At baseline, compound brain volume (brain volume in the z block [BVz] = cGM + dGM + WM) correlated with SIENAX-normalized brain volume ( = 0.938, < 0.001); percentage change from baseline in BVz over 2 years correlated with structural image evaluation using normalization of atrophy percentage brain volume change ( = 0.713, < 0.001). For placebo, volume reductions were most pronounced in cGM, and relative changes from baseline were strongest in dGM. Over 24 months, there were significant reductions with fingolimod vs placebo for dGM (0.5 mg -14.5%, = 0.017; 1.25 mg -26.6%, < 0.01) and thalamus (0.5 mg -26.1%, = 0.006; 1.25 mg -49.7%, < 0.001). Reduction of cGM volume loss was not significant. Significantly less WM loss and VV enlargement were seen with fingolimod vs placebo (all < 0.001). A high T2 lesion volume at baseline predicted on-study cGM, dGM, and thalamic volume loss ( < 0.0001) but not WM loss. Patients taking placebo with high dGM (hazard ratio [HR] 0.54, = 0.0323) or thalamic (HR 0.58, = 0.0663) volume at baseline were less likely to show future disability worsening.
CONCLUSIONS
Fingolimod significantly reduced dGM volume loss (including thalamus) vs placebo in patients with RRMS. Reducing dGM and thalamic volume loss might improve long-term outcome.
目的
研究芬戈莫德对复发缓解型多发性硬化症（RRMS）患者的深部灰质（dGM）、丘脑、皮质灰质（cGM）、白质（WM）和脑室容积（VV）的影响。
方法
数据来自两项 3 期研究的汇总。共有 2355 名患者中的 2064 名（88%）参与了分析：芬戈莫德 0.5mgn=783 名，芬戈莫德 1.25mgn=799 名，或安慰剂 n=773 名。使用 FMRIB 的集成注册和分割工具评估 dGM 和丘脑体积的基线百分比变化；使用结构图像评估使用归一化萎缩横断面版本（SIENAX）在 12 个月和 24 个月评估 WM、cGM 和 VV。
结果
在基线时，复合脑体积（z 块中的脑体积[BVz]=cGM+dGM+WM）与 SIENAX 归一化脑体积相关（=0.938，<0.001）；两年内 BVz 的基线百分比变化与使用归一化萎缩百分比脑体积变化的结构图像评估相关（=0.713，<0.001）。对于安慰剂，cGM 中的体积减少最为明显，而 dGM 的基线相对变化最强。在 24 个月时，与安慰剂相比，芬戈莫德显著降低了 dGM（0.5mg-14.5%，=0.017；1.25mg-26.6%，<0.01）和丘脑（0.5mg-26.1%，=0.006；1.25mg-49.7%，<0.001）。cGM 体积损失减少不显著。与安慰剂相比，芬戈莫德组 WM 损失和 VV 增大显著减少（均<0.001）。基线时高 T2 病变体积预测研究中的 cGM、dGM 和丘脑体积损失（<0.0001），但不预测 WM 损失。基线时 dGM（危险比[HR]0.54，=0.0323）或丘脑（HR0.58，=0.0663）体积较高的安慰剂患者不太可能出现未来残疾恶化。
结论
在 RRMS 患者中，芬戈莫德显著降低了 dGM 体积损失（包括丘脑），与安慰剂相比。减少 dGM 和丘脑体积损失可能会改善长期预后。
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