Outcomes after 18 months of eliglustat therapy in treatment-naïve adults with Gaucher disease type 1: The phase 3 ENGAGE trial.
Outcomes after 18 months of eliglustat therapy in treatment-naïve adults with Gaucher disease type 1: The phase 3 ENGAGE trial.
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DOI：
10.1002/ajh.24877
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发表时间：
2017-11
影响因子：
12.8
通讯作者：
Peterschmitt MJ
中科院分区：
文献类型：
--
作者：
Mistry PK;Lukina E;Ben Turkia H;Shankar SP;Baris H;Ghosn M;Mehta A;Packman S;Pastores G;Petakov M;Assouline S;Balwani M;Danda S;Hadjiev E;Ortega A;Gaemers SJM;Tayag R;Peterschmitt MJ
Eliglustat是一种口服底物减少疗法，是1型戈谢病（GD 1）成人患者的一线治疗，这些患者为CYP2D6弱、中度或强代谢者（>90%的患者）。在III期ENGAGE试验（NCT 00891202）的主要分析中，与安慰剂相比，eliglustat治疗9个月导致脾脏和肝脏体积显著减少，血红蛋白浓度和血小板计数增加。我们报告了进入试验扩展期的患者的18个月结局，所有患者均接受了eliglustat治疗。在40例试验患者中，39例进入扩展期，38例完成18个月。确定脾脏和肝脏体积、血红蛋白浓度、血小板计数、骨矿物质密度、骨髓负荷和戈谢病生物标志物的绝对值和随时间的百分比变化。对于在双盲期随机接受eliglustat的患者，继续接受eliglustat治疗9个月以上导致所有疾病参数的增量改善。对于在双盲期随机分配至安慰剂组的患者，9个月开放标签期内的eliglustat治疗导致脾脏和肝脏体积显著减少，血红蛋白和血小板显著增加，变化率与在双盲期接受eliglustat的患者相似。Eliglustat治疗还与骨髓负荷评分、骨矿物质密度和戈谢病既定生物标志物（包括生物活性脂质、葡萄糖鞘氨醇减少）的改善相关。这些结果强调了eliglustat在初治患者中的疗效。Eliglustat耐受性良好，长期暴露未出现新的安全性问题。
Eliglustat, an oral substrate reduction therapy, is a first‐line treatment for adults with Gaucher disease type 1 (GD1) who are poor, intermediate, or extensive CYP2D6 metabolizers (>90% of patients). In the primary analysis of the Phase 3 ENGAGE trial (NCT00891202), eliglustat treatment for 9 months resulted in significant reductions in spleen and liver volumes and increases in hemoglobin concentration and platelet count compared with placebo. We report 18‐month outcomes of patients who entered the trial extension period, in which all patients received eliglustat. Of 40 trial patients, 39 entered the extension period, and 38 completed 18 months. Absolute values and percent change over time were determined for spleen and liver volume, hemoglobin concentration, platelet count, bone mineral density, bone marrow burden, and Gaucher disease biomarkers. For patients randomized to eliglustat in the double‐blind period, continuing treatment with eliglustat for 9 more months resulted in incremental improvement of all disease parameters. For patients randomized to placebo in the double‐blind period, eliglustat treatment during the 9‐month, open‐label period resulted in significant decrease of spleen and liver volumes and significant increase of hemoglobin and platelets, with a similar rate of change to patients who had received eliglustat in the double‐blind period. Eliglustat treatment was also associated with improvement in bone marrow burden score, bone mineral density, and established biomarkers of Gaucher disease, including reduction of the bioactive lipid, glucosylsphingosine. These findings underscore the efficacy of eliglustat in treatment‐naïve patients. Eliglustat was well‐tolerated, and there were no new safety concerns with longer‐term exposure.
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影响因子：
12.8
作者：
Murugesan V;Chuang WL;Liu J;Lischuk A;Kacena K;Lin H;Pastores GM;Yang R;Keutzer J;Zhang K;Mistry PK
通讯作者：
Mistry PK
DOI：
10.1056/nejmoa1508808
发表时间：
2016-02-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Nair S;Branagan AR;Liu J;Boddupalli CS;Mistry PK;Dhodapkar MV
通讯作者：
Dhodapkar MV
影响因子：
2.3
作者：
Lukina, Elena;Watman, Nora;Peterschmitt, Judith M.
通讯作者：
Peterschmitt, Judith M.
DOI：
10.1073/pnas.1003308107
发表时间：
2010-11-09
影响因子：
11.1
作者：
Mistry, Pramod K.;Liu, Jun;Zaidi, Mone
通讯作者：
Zaidi, Mone
影响因子：
20.3
作者：
Cox, Timothy M.;Drelichman, Guillermo;Peterschmitt, M. Judith
通讯作者：
Peterschmitt, M. Judith