Treatment of Wilson disease with ammonium tetrathiomolybdate - III. Initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapy
Treatment of Wilson disease with ammonium tetrathiomolybdate - III. Initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapy
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DOI：
10.1001/archneur.60.3.379
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发表时间：
2003-03-01
影响因子：
--
通讯作者：
Fink, JK
中科院分区：
文献类型：
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作者：
Brewer, GJ;Hedera, P;Fink, JK
背景：尚不清楚对于出现神经系统症状的威尔逊病患者应使用哪种抗铜药物，因为青霉胺常常使他们的神经系统恶化，而锌起效缓慢。目的：评估四硫代钼酸铵神经系统恶化的频率和药物不良反应。设计：对 55 名未经治疗的患有神经系统威尔逊病的患者（其中 22 名新患者）进行开放标签研究，接受四硫代钼酸盐治疗，剂量从 120 到 120 不等。 410 mg/d，持续 8 周，然后随访 3 年。通过神经系统和言语测试评分来评估神经功能。设置：大学医院转诊环境。患者：所有未经治疗的新诊断神经系统威尔逊病患者。干预：用四硫代钼酸盐治疗。主要结果指标：通过神经系统和言语检查评估神经功能。通过全血细胞计数和生化测量来评估药物不良反应。结果：在接受四硫代钼酸盐治疗的 55 名患者中，只有 2 名 (4%) 出现神经功能恶化，而接受青霉胺治疗的患者中估计有 50% 的患者出现神经功能恶化。 22 名新患者中有 5 名出现骨髓抑制，3 名出现转氨酶升高。这些数字高于最初的 33 名患者，似乎主要是由于更快速的剂量递增。结论：四硫代钼酸盐对出现神经系统表现的威尔逊病患者显示出优异的疗效。随着剂量的快速增加，可能会出现骨髓抑制或转氨酶升高的不良反应。
Background: It is unclear what anticopper drug to use for patients with Wilson disease who present with neurologic manifestations because penicillamine often makes them neurologically worse and zinc is slow acting.Objective: To evaluate the frequency of neurologic worsening and drug adverse effects with ammonium tetrathiomolybdate.Design: Open-label study of 55 untreated patients (22 of them new) presenting with neurologic Wilson disease treated with tetrathiomolybdate varying from 120 to 410 mg/d for 8 weeks and then followed up for 3 years. Neurologic function was assessed with scored neurologic and speech tests.Setting: A university hospital referral setting.Patients: All untreated, newly diagnosed patients with neurologic Wilson disease.Intervention: Treatment with tetrathiomolybdate.Main Outcome Measures: Neurologic function was evaluated by neurologic and speech examinations. Drug adverse effects were evaluated by complete blood cell counts and biochemical measures.Results: Only 2 (4%) of 55 patients treated with tetrathiomolybdate showed neurologic deterioration, compared with an estimated 50% of penicillamine-treated patients. Five of the 22 new patients exhibited bone marrow suppression and 3 had aminotransferase elevations. These numbers are higher than in the original 33 patients and appear to be due primarily to a more rapid dose escalation.Conclusions: Tetrathiomolybdate shows excellent efficacy in patients with Wilson disease who present with neurologic manifestations. With rapid escalation of dose, adverse effects from bone marrow suppression or aminotransferase elevations can occur.