Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat.
Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat.
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Gaucher疾病1型患者的骨骼改善：口服Eliglustat的2期试验。
DOI：
10.1007/s00256-014-1891-9
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发表时间：
2014-10
影响因子：
2.1
通讯作者：
Rosenthal, Daniel I.
中科院分区：
文献类型：
--
作者：
Kamath, Ravi S.;Lukina, Elena;Watman, Nora;Dragosky, Marta;Pastores, Gregory M.;Avila Arreguin, Elsa;Rosenbaum, Hanna;Zimran, Ari;Aguzzi, Rasha;Puga, Ana Cristina;Norfleet, Andrea M.;Peterschmitt, M. Judith;Rosenthal, Daniel I.
关键词：
Eliglustat是一种用于1型戈谢病（GD 1）的研究性口服底物减少疗法。在一项开放标签、多中心、单臂II期试验（NCT 00358150）中，通过前瞻性监测骨矿物质密度（BMD）、骨折、戈谢细胞骨髓浸润、局灶性骨病变和梗死，评价其骨骼效应。获得机构审查委员会批准和患者知情同意。Eliglustat（50或100 mg）每日两次口服自我给药; 19例患者完成了4年治疗。所有患者均为生殖成熟（年龄范围，18-55岁）。在基线时进行DXA和MRI评估，此后每年进行一次。每年进行一次X线检查，直到第24个月，然后每隔一年进行一次。腰椎BMD从基线至第4年显著增加（p = 0.02; n = 15），平均（SD）为9.9%（14.2%）;相应的T评分从平均（SD）-1.6（1.1）显著增加（p = 0.01）至-0.9（1.3）。平均股骨T评分在4年内保持正常。股骨MRI显示，10/18例（56%）患者的戈谢细胞浸润较基线减少; 1例早期改善的患者在第4年出现一过性恶化。研究期间未发生腰椎或股骨骨折，也未报告骨危象。基线时，8/19例（42%）患者有局灶性骨病变，保持稳定，7/19例（37%）患者有骨梗死，1例患者在第2年时改善。在第4年，发现1例新的无症状、不确定的骨病变，随后消退。Eliglustat可能是治疗GD 1骨骼表现的一种治疗选择。
Eliglustat is an investigational oral substrate reduction therapy for Gaucher disease type 1 (GD1). Its skeletal effects were evaluated by prospective monitoring of bone mineral density (BMD), fractures, marrow infiltration by Gaucher cells, focal bone lesions, and infarcts during an open-label, multi-site, single-arm phase 2 trial (NCT00358150). Institutional review board approval and patient informed consent were obtained. Eliglustat (50 or 100 mg) was self-administered by mouth twice daily; 19 patients completed 4 years of treatment. All were skeletally mature (age range, 18–55 years). DXA and MRI assessments were conducted at baseline and annually thereafter. X-rays were obtained annually until month 24, and then every other year. Lumbar spine BMD increased significantly (p = 0.02; n = 15) by a mean (SD) of 9.9 % (14.2 %) from baseline to year 4; corresponding T-scores increased significantly (p = 0.01) from a mean (SD) of −1.6 (1.1) to −0.9 (1.3). Mean femur T-score remained normal through 4 years. Femur MRI showed that 10/18 (56 %) patients had decreased Gaucher cell infiltration compared to baseline; one patient with early improvement had transient worsening at year 4. There were no lumbar spine or femoral fractures and no reported bone crises during the study. At baseline, 8/19 (42 %) patients had focal bone lesions, which remained stable, and 7/19 (37 %) patients had bone infarctions, which improved in one patient by year 2. At year 4, one new asymptomatic, indeterminate bone lesion was discovered that subsequently resolved. Eliglustat may be a therapeutic option for treating the skeletal manifestations of GD1.
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影响因子：
3.2
作者：
Pastores, Gregory M.;Elstein, Deborah;Zimran, Ari
通讯作者：
Zimran, Ari
影响因子：
2.3
作者：
Lukina, Elena;Watman, Nora;Peterschmitt, Judith M.
通讯作者：
Peterschmitt, Judith M.
影响因子：
5.8
作者：
van Dussen, L.;Lips, P.;Hollak, C. E. M.
通讯作者：
Hollak, C. E. M.
影响因子：
2.3
作者：
Dahl, Stephan vom;Poll, Ludger;Maas, Mario
通讯作者：
Maas, Mario
影响因子：
2.6
作者：
Maas, M;Poll, LW;Terk, MR
通讯作者：
Terk, MR