Eliglustat maintains long-term clinical stability in patients with Gaucher disease type 1 stabilized on enzyme therapy
Eliglustat maintains long-term clinical stability in patients with Gaucher disease type 1 stabilized on enzyme therapy
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DOI：
10.1182/blood-2016-12-758409
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发表时间：
2017-04-27
期刊：
影响因子：
20.3
通讯作者：
Peterschmitt, M. Judith
中科院分区：
文献类型：
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作者：
Cox, Timothy M.;Drelichman, Guillermo;Peterschmitt, M. Judith
在采用酶替代治疗达到治疗目标的戈谢病患者中开展的III期酒石酸依格列他（Genz-112638）研究（ENCORE）中，1年时，依格列他在维持稳定的血小板计数、血红蛋白浓度以及脾脏和肝脏体积方面非劣效于伊米苷酶治疗。在该主要分析期后，患者进入长期扩展期，所有患者均接受eliglustat治疗。eliglustat的持续时间范围为2至5年，具体取决于入组时间（跨越2年）、患者随机分配的治疗组以及当市售eliglustat上市时他们是否居住在美国。在这里，我们报告了在ENCORE试验中接受eliglustat的157例患者的eliglustat的长期安全性和疗效; 46例接受eliglustat 4年的患者的数据可用。平均血红蛋白浓度、血小板计数、脾脏和肝脏体积保持稳定长达4年。年复一年，所有4项指标在>= 85%的患者中总体保持稳定（复合终点相对于基线值），在>= 92%的患者中单独保持稳定。平均骨矿物质密度z评分（腰椎和股骨）保持稳定，并始终保持在健康参考范围内。4年内，Eliglustat耐受性良好; 4例（2.5%）患者因认为与研究药物相关的不良事件退出研究。未发现新的或长期的安全性问题。在ENCORE试验中接受eliglustat治疗长达4年的1型戈谢病成人中，通过复合和个体指标评估的临床稳定性得以维持。
In the phase 3 Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease Who Have Reached Therapeutic Goals With Enzyme Replacement Therapy (ENCORE), at 1 year, eliglustat was noninferior to imiglucerase enzyme therapy in maintaining stable platelet counts, hemoglobin concentrations, and spleen and liver volumes. After this primary analysis period, patients entered a long-term extension phase in which all received eliglustat. Duration on eliglustat ranged from 2 to 5 years, depending on timing of enrollment (which spanned 2 years), treatment group to which patients were randomized, and whether they lived in the United States when commercial eliglustat became available. Here we report long-term safety and efficacy of eliglustat for 157 patients who received eliglustat in the ENCORE trial; data are available for 46 patients who received eliglustat for 4 years. Mean hemoglobin concentration, platelet count, and spleen and liver volumes remained stable for up to 4 years. Year to year, all 4 measures remained collectively stable (composite end point relative to baseline values) in >= 85% of patients as well as individually in >= 92%. Mean bone mineral density z scores (lumbar spine and femur) remained stable and were maintained in the healthy reference range throughout. Eliglustat was well tolerated over 4 years; 4 (2.5%) patients withdrew because of adverse events that were considered related to the study drug. No new or long-term safety concerns were identified. Clinical stability assessed by composite and individual measures was maintained in adults with Gaucher disease type 1 treated with eliglustat who remained in the ENCORE trial for up to 4 years.