Enzyme-replacement therapy with agalsidase alfa in children with Fabry disease
Enzyme-replacement therapy with agalsidase alfa in children with Fabry disease
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DOI：
10.1542/peds.2005-2895
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发表时间：
2006-09-01
期刊：
影响因子：
8
通讯作者：
Schiffmann, Raphael
中科院分区：
文献类型：
--
作者：
Ries, Markus;Clarke, Joe T. R.;Schiffmann, Raphael
上下文法布里病是一种X连锁多系统疾病。成人的酶替代疗法在治疗晚期法布里病的主要后遗症（如肾衰竭或中风）方面疗效有限。这促使了一项关于在法布里病早期阶段酶替代的安全性和有效性的研究。本研究的目的是评价半乳糖苷酶α酶治疗法布雷病患儿的安全性和疗效。我们在3个三级护理中心进行了一项为期6个月的开放标签研究，共有24名儿童（19名男孩和5名女孩），平均年龄为11.8岁（范围：6.5 - 18岁），以检查安全性参数，包括输液反应和抗半乳糖苷酶α抗体。我们在3个三级护理中心对24名平均年龄为11.8岁（范围：6.5-18岁）的儿童（19名男孩和5名女孩）进行了一项为期6个月的开放标签研究，以检查安全性参数，包括输注反应和抗半乳糖苷酶α抗体。半乳糖苷酶α耐受性良好，所有患者均完成了研究。6名男孩和1名女孩出现轻度至中度输注反应。1例男孩出现抗半乳糖苷酶α的一过性免疫球蛋白G抗体。治疗后，男孩的血浆神经酰胺三己糖苷显著降低。平均估计肾小球滤过率、心脏结构和功能正常，26周内未发生变化。通过2小时动态监测确定的心率变异性，在基线时男孩比女孩降低。男孩的心率变异性的所有指标都有显著改善。三个无汗症患者，通过定量的汗腺轴突反射测试确定，出汗。11例患者中有6例可以减少或停止使用抗神经病镇痛药。在本研究中，用半乳糖苷酶α替代酶是安全的。探索性疗效分析记录了神经酰胺三己糖苷清除率增加和自主神经功能改善。需要进行前瞻性的长期研究，以评估法布里病患者早期开始的酶替代是否能够预防成年后的主要器官衰竭。
CONTEXT. Fabry disease is an X-linked multisystem disorder. Enzyme-replacement therapy in adults has limited efficacy in treating major sequelae of advanced Fabry disease, such as kidney failure or stroke. This prompted a study of the safety and efficacy of enzyme replacement at an earlier stage of Fabry disease.OBJECTIVES. Our purpose with this work was to evaluate safety and to explore efficacy of enzyme treatment with agalsidase alfa in pediatric patients with Fabry disease.METHODS. We conducted a 6-month open-label study at 3 tertiary care centers with 24 children (19 boys and 5 girls) with a mean age of 11.8 (range: 6.5 - 18) years, to examine safety parameters, including infusion reactions and antiagalsidase alfa antibodies.METHODS. We conducted a 6-month open-label study at 3 tertiary care centers with 24 children (19 boys and 5 girls) with a mean age of 11.8 (range: 6.5-18) years, to examine safety parameters, including infusion reactions and antiagalsidase alfa antibodies.RESULTS. Agalsidase alfa was well tolerated, and all of the patients completed the study. Six boys and 1 girl had mild-to-moderate infusion reactions. One boy developed transient immunoglobulin G antibodies against agalsidase alfa. The boys showed a significant reduction in plasma globotriaosylceramide on treatment. Mean estimated glomerular filtration rate, cardiac structure, and function were normal and did not change over 26 weeks. Heart rate variability, as determined by 2-hour ambulatory monitoring, was decreased in the boys compared with the girls at baseline. All indices of heart rate variability improved significantly in the boys. Three patients with anhidrosis, as determined by quantitative sudomotor axon reflex testing, developed sweating. Six of 11 patients could reduce or cease their use of antineuropathic analgesics.CONCLUSIONS. Enzyme replacement with agalsidase alfa was safe in this study. The exploratory efficacy analysis documented increased clearance of globotriaosylceramide and improvement of autonomic function. Prospective long-term studies are needed to assess whether enzyme replacement initiated early in patients with Fabry disease is able to prevent major organ failure in adulthood.