A pilot trial of ocrelizumab for modulation of meningeal enhancement in multiple sclerosis.
A pilot trial of ocrelizumab for modulation of meningeal enhancement in multiple sclerosis.
复制标题
ocrelizumab 用于调节多发性硬化症脑膜增强的初步试验。
DOI：
10.1016/j.msard.2023.105344
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发表时间：
2024
影响因子：
4
通讯作者：
Harrison,DanielM
中科院分区：
文献类型：
--
作者：
Dahal,Shishir;Allette,YohanceM;Naunton,Kerry;Harrison,DanielM
背景尸检数据表明多发性硬化（MS）的脑膜炎症是由CD 20 + B细胞驱动的。Ocrelizumab是一种抗CD 20单克隆抗体，因此可以潜在地改善MS中的脑膜炎症。MRI上的软脑膜增强（LME）被认为是MS中脑膜炎症的替代生物标志物，因此可能是监测这种治疗效果的一种方法。目的为了确定ocrelizumab是否影响MS中7 T MRI上的脑膜增强（ME）。两名MS患者由他们的治疗医生开始接受ocrelizumab治疗，被纳入该单中心、开放标签、前瞻性试验。参与者在第一次输注前接受了脑部的7 T MRI，并筛查了LME的存在。14名患者（48 ± 11岁; 11名女性）在基线扫描时患有LME，并被邀请在治疗1年后返回进行额外的7 T MRI。来自一个单独的年度7 T MRI观察性队列的14例接受非CD 20治疗的MS患者（49 ± 10岁; 11例女性）用于基线、年龄和性别时LME的比较匹配。对比后FLAIR和减影图像进行审查LME和血管旁和硬膜增强（PDE）。ResultsAll科目ocrelizumab和对照组有LME和PDE的基线扫描。在研究开始时，研究组中LME和PDE病灶的平均数量分别为2.3 ± 1.7和6.6 ± 3.9。对照组的平均LME和PDE计数分别为1.7 ± 1.5和7.8 ± 5.5。研究组中LME的平均体积为50.5 mm 3 ± 65.0 mm 3，PDE的平均体积为866 mm 3 ± 937.9 mm 3。对照组LME和PDE的平均体积分别为28.4 mm 3 ± 36.0和885 mm 3 ± 947.7。随访时，两组中LME患者的数量均减少至8例（57%），而PDE患者的比例无变化。在研究组（0.07 ± 2.9，p = 0.97）和对照组（-0.71 ± 1.5，p = 0.08）中均观察到1年后LME数量的最小平均变化。两个研究组的LME体积平均变化最小（-21.91 mm 3 ± 77.66，p = 0.27）和对照组（3.4 mm ~ 3 ± 32.11，p = 0.77），两组患者术后1年平均PDE病灶数变化不大（-0.71 ± 2.36，p = 0.32）和对照组（-0.17 ± 3.89，p = 0.15）。PDE体积的平均变化是可测量的，但在两个研究组中均不显著（-397.1 mm3±959.6，p = 0.80）和对照组（-417.0 mm3± 922.7）（p = 0.80）。研究中LME和PDE的病灶计数和体积变化与对照组相比无显著差异。在初步试验中，ocrelizumab没有显著减少MS患者中LME或PDE病灶的数量或体积。
BackgroundAutopsy data suggests that meningeal inflammation in multiple sclerosis (MS) is driven by CD20+ B-cells. Ocrelizumab is an anti-CD20 monoclonal antibody, and thus could potentially ameliorate meningeal inflammation in MS. Leptomeningeal enhancement (LME) on MRI is suggested as a surrogate biomarker of meningeal inflammation in MS, and thus may be a way of monitoring for this treatment effect.ObjectivesTo determine if ocrelizumab impacts meningeal enhancement (ME) on 7T MRI in MS.MethodsTwenty-two patients with MS started on ocrelizumab by their treating physician were enrolled into this single-center, open-label, prospective trial. Participants underwent 7T MRI of the brain prior to first infusion, with screening for the presence of LME. Fourteen patients (48 ± 11 years; 11 women) had LME on the baseline scan and were invited to return for an additional 7T MRI after 1 year of treatment. Fourteen MS patients (49 ± 10 years; 11 women) on non-CD20 treatment from a separate observational cohort of annual 7T MRIs were used for comparison – matched for LME at baseline, age, and sex. Post-contrast FLAIR and subtraction images were reviewed for LME and paravascular and dural enhancement (PDE).ResultsAll subjects in the ocrelizumab and comparison groups had LME and PDE on their baseline scan. At the beginning of the study the mean number of foci of LME and PDE in the study group were 2.3 ± 1.7 and 6.6 ± 3.9 respectively. Mean LME and PDE count for the comparison group were 1.7 ± 1.5 and 7.8 ± 5.5. Mean volume of LME in the study group was 50.5 mm3± 65.0 mm3and that of the PDE was 866 mm3± 937.9. Mean volume of LME and PDE for comparison group were 28.4 mm3± 36.0 and 885 mm3± 947.7 respectively.At follow-up, the number of patients with LME decreased to 8 (57 %) in both groups, whereas the proportion of patients with PDE was unchanged. Minimal mean change in the number of LME after 1 year were seen in both the study group (0.07 ± 2.9, p = 0.97) and comparison group (-0.71 ± 1.5, p = 0.08). Minimal mean change was seen in the volume of LME in both the study group (-21.91 mm3± 77.66, p = 0.27) and comparison group (3.4 mm3± 32.11, p = 0.77).There was minimal change in the mean number of foci of PDE after 1 year in both the study group (-0.71 ± 2.36, p = 0.32) and in the comparison group (-0.17 ± 3.89, p = 0.15). Mean change in volume of PDE was measurable, but not significant in both the study group (-397.1 mm3±959.6, p = 0.80) and in the comparison group (-417.0 mm3± 922.7) (p = 0.80).Comparisons between the changes in foci count and volume for both LME and PDE in the study versus comparison groups showed no significant differences.ConclusionIn this small pilot trial, ocrelizumab did not significantly reduce the number or volume of foci of LME or PDE in MS patients.