Zimran Ari, Gonzalez-Rodriguez Derlis Emilio, Abrahamov Aya, Elstein Deborah, Paz Alona, Brill-Almon Einat, Chertkoff Raul
Gaucher Clinic, Shaare Zedek Medical Center, 12 Bayit Street, Jerusalem 01931, Israel; Hadassah Medical School - Hebrew University, Jerusalem, Israel.
Instituto Privado de Hematologia e Investigacion Clinica (I.P.H.I.C.), Asuncion, Paraguay.
Blood Cells Mol Dis. 2015 Jan;54(1):9-16. doi: 10.1016/j.bcmd.2014.10.002. Epub 2014 Nov 7.
Taliglucerase alfa is a plant cell-expressed beta-glucocerebrosidase approved in the United States, Israel, Australia, Canada, and other countries for enzyme replacement therapy in adults with Type 1 Gaucher disease (GD), for treatment of pediatric patients in the United States, Australia, and Canada, and for the hematologic manifestations of Type 3 GD in pediatric patients in Canada. This multicenter, randomized, double-blind, parallel-dose, 12-month study assessed efficacy and safety of taliglucerase alfa in pediatric patients with GD. Eleven children were randomized to taliglucerase alfa 30U/kg (n=6) or 60U/kg (n=5) per infusion every other week. From baseline to month 12, the following changes were noted in the taliglucerase alfa 30-U/kg and 60-U/kg dose groups, respectively: median hemoglobin concentrations increased by 12.2% and 14.2%; the interquartile ranges of median percent change in hemoglobin levels from baseline were 20.6 and 10.4, respectively; mean spleen volume decreased from 22.2 to 14.0 multiples of normal (MN) and from 29.4 to 12.9 MN; mean liver volume decreased from 1.8 to 1.5 MN and from 2.2 to 1.7 MN; platelet counts increased by 30.9% and 73.7%; and chitotriosidase activity was reduced by 58.5% and 66.1%. Nearly all adverse events were mild/moderate, unrelated to treatment, and transient. One patient presented with treatment-related gastroenteritis reported as a serious adverse event due to the need for hospitalization for rehydration. No patient discontinued. These data suggest that taliglucerase alfa has the potential to be a therapeutic treatment option for children with GD. This study was registered at www.clinicaltrials.gov as NCT01132690.
他利糖酶α是一种在植物细胞中表达的β-葡萄糖脑苷脂酶，已在美国、以色列、澳大利亚、加拿大和其他国家获批，用于1型戈谢病（GD）成人患者的酶替代疗法，在美国、澳大利亚和加拿大用于治疗儿科患者，在加拿大用于治疗儿科3型GD的血液学表现。这项多中心、随机、双盲、平行剂量、为期12个月的研究评估了他利糖酶α在儿科GD患者中的疗效和安全性。11名儿童被随机分为每两周输注一次他利糖酶α，剂量为30U/kg（n = 6）或60U/kg（n = 5）。从基线到第12个月，他利糖酶α 30-U/kg和60-U/kg剂量组分别出现了以下变化：血红蛋白浓度中位数分别增加了12.2%和14.2%；血红蛋白水平自基线起变化百分比中位数的四分位间距分别为20.6和10.4；平均脾脏体积从正常的22.2倍降至14.0倍，从29.4倍降至12.9倍；平均肝脏体积从1.8倍降至1.5倍，从2.2倍降至1.7倍；血小板计数分别增加了30.9%和73.7%；壳三糖苷酶活性分别降低了58.5%和66.1%。几乎所有不良事件均为轻度/中度，与治疗无关且为短暂性。有1名患者出现与治疗相关的肠胃炎，因需要住院补液而被报告为严重不良事件。没有患者停药。这些数据表明，他利糖酶α有可能成为治疗儿童GD的一种治疗选择。本研究已在www.clinicaltrials.gov上注册为NCT01132690。
