Belimumab for the Treatment of Early Diffuse Systemic Sclerosis: Results of a Randomized, Double-Blind, Placebo-Controlled, Pilot Trial.
Belimumab for the Treatment of Early Diffuse Systemic Sclerosis: Results of a Randomized, Double-Blind, Placebo-Controlled, Pilot Trial.
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DOI：
10.1002/art.40358
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Spiera RF
中科院分区：
文献类型：
--
作者：
Gordon JK;Martyanov V;Franks JM;Bernstein EJ;Szymonifka J;Magro C;Wildman HF;Wood TA;Whitfield ML;Spiera RF
评估贝利木单抗治疗早期弥漫性皮肤系统性硬化症（dcSSc）患者的安全性和疗效，这些患者接受了背景治疗吗替麦考酚酯（MMF）。在这项为期52周、促炎剂启动、单中心、双盲、安慰剂对照、初探性研究中，20例近期开始接受MMF治疗的dcSSc患者以1：1的比例随机接受额外贝利木单抗10 mg/kg静脉给药或安慰剂治疗。我们评估了安全性、有效性和差异基因表达。贝利木单抗组中，改良Rodnan皮肤厚度评分（MRSS）中位数从27（四分位距[IQR] 26.5，31）降至18（IQR 11，23）（P = 0.039）。在安慰剂组中，中位MRSS从28（IQR 22，28）降至21（IQR 14，25）（P = 0.023）。贝利木单抗组MRSS的中位变化为−10（IQR −13，−9），安慰剂组为−3.0（IQR −15，−1）（P = 0.411）。两组间不良事件（AE）数量无显著差异。在贝利木单抗组MRSS改善的患者中观察到B细胞信号传导和促纤维化基因和途径的表达显著降低，但在安慰剂组中未观察到。两个治疗组的患者均经历了MRSS的显著改善。贝利木单抗组的中位差异更大，但在这项小型初探性研究中未达到统计学显著性。两组之间的AE相似。基因表达的变化与作用机制一致，表明贝利木单抗治疗的临床应答与促纤维化基因和途径的显著减少相关。需要进行额外的研究来确定贝利木单抗在dcSSc治疗中的作用。
To assess the safety and efficacy of treatment with belimumab in patients with early diffuse cutaneous systemic sclerosis (dcSSc) treated with background mycophenolate mofetil (MMF). In this 52-week, investigator-initiated, single-center, double-blind, placebo-controlled, pilot study, 20 patients with dcSSc recently started on MMF were randomized 1:1 to additionally receive belimumab at 10 mg/kg intravenously or placebo. We assessed safety, efficacy, and differential gene expression. In the belimumab group, the median modified Rodnan skin thickness score (MRSS) decreased from 27 (interquartile range [IQR] 26.5, 31) to 18 (IQR 11, 23) (P = 0.039). In the placebo group, the median MRSS decreased from 28 (IQR 22, 28) to 21 (IQR 14, 25) (P = 0.023). The median change in MRSS was −10 (IQR −13, −9) in the belimumab group and −3.0 (IQR −15, −1) in the placebo group (P = 0.411). There were no significant differences between the groups in the number of adverse events (AEs). A significant decrease in expression of B cell signaling and profibrotic genes and pathways was observed in patients with improved MRSS in the belimumab group but not in the placebo group. Patients in both treatment groups experienced significant improvements in MRSS. The median difference was greater in the belimumab group but did not achieve statistical significance in this small pilot study. AEs were similar between the groups. Changes in gene expression were consistent with mechanism of action and showed that clinical response to treatment with belimumab is associated with a significant decrease in profibrotic genes and pathways. Additional studies are needed to determine the role of belimumab in the treatment of dcSSc.
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影响因子：
4.9
作者：
François A;Chatelus E;Wachsmann D;Sibilia J;Bahram S;Alsaleh G;Gottenberg JE
通讯作者：
Gottenberg JE
影响因子：
6.5
作者：
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5.5
作者：
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通讯作者：
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