Treatment of Wilson disease with ammonium tetrathiomolybdate - IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease
Treatment of Wilson disease with ammonium tetrathiomolybdate - IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease
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DOI：
10.1001/archneur.63.4.521
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发表时间：
2006-04-01
影响因子：
--
通讯作者：
Sitterly, J
中科院分区：
文献类型：
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作者：
Brewer, GJ;Askari, F;Sitterly, J
目的：比较四硫代钼酸盐和曲恩汀治疗患有威尔逊病神经系统表现的患者的神经系统恶化频率、不良反应和神经系统恢复程度。 设计：一项随机、双盲、对照、2组研究，纳入了 48 名患有威尔逊病神经系统表现的患者。患者要么随餐服用 500 mg 盐酸曲恩汀，每天 2 次，要么服用 20 mg 四硫代钼酸盐，每天 3 次，随餐服用；20 mg，每天 3 次，两餐之间服用，持续 8 周。所有患者每天服用 2 次 50 毫克锌。患者住院8周，每周评估神经系统和言语功能；出院时每天服用 50 毫克锌 3 次，每年返回进行随访。地点：大学医院转诊环境。患者：主要是新诊断的威尔逊病患者，出现神经系统症状，且未使用抗铜药物治疗超过 4 周。干预：用曲恩汀加锌或四硫代钼酸盐加锌治疗。主要结果指标：神经功能通过以下指标评估： 半定量神经学和言语检查。通过血细胞计数和生化指标评估药物不良事件。结果：曲恩汀组 23 名患者中有 6 名，四硫代钼酸盐组 25 名患者中有 1 名出现神经功能恶化（P < .05）。接受四硫代钼酸盐治疗的 3 名患者出现贫血和/或白细胞减少的不良反应，4 名患者出现转氨酶进一步升高。一名接受曲恩汀治疗的患者出现了贫血的不良反应。 4 名接受曲恩汀治疗的患者在随访期间死亡，其中 3 名患者最初表现出神经功能恶化。 3 年随访期间，神经系统和语言功能恢复得相当好。结论：对于患有神经系统疾病的患者，四硫代钼酸盐是比曲恩汀更好的保留神经功能的选择。
Objective: To compare tetrathiomolybdate and trientine in treating patients with the neurologic presentation of Wilson disease for the frequency of neurologic worsening, adverse effects, and degree of neurologic recovery.Design: A randomized, double-blind, controlled, 2-arm study of 48 patients with the neurologic presentation of Wilson disease. Patients either received 500 mg of trientine hydrochloride 2 times per day or 20 mg of tetrathiomolybdate 3 times per day with meals and 20 mg 3 times per day between meals for 8 weeks. All patients received 50 mg of zinc 2 times per day. Patients were hospitalized for 8 weeks, with neurologic and speech function assessed weekly; discharged taking 50 mg of zinc 3 times per day, and returned annually for follow-up.Setting: A university hospital referral setting.Patients: Primarily newly diagnosed patients with Wilson disease presenting with neurologic symptoms who had not been treated longer than 4 weeks with an anti-copper drug.Intervention: Treatment with either trientine plus zinc or tetrathiomolybdate plus zinc.Main Outcome Measures: Neurologic function was assessed by semiquantitative neurologic and speech examinations. Drug adverse events were evaluated by blood cell counts and biochemical measures.Results: Six of 23 patients in the trientine arm and 1 of 25 patients in the tetrathiomolybdate arm under-went neurologic deterioration (P < .05). Three patients receiving tetrathiomolybdate had adverse effects of anemia and/or leukopenia, and 4 had further transaminase elevations. One patient receiving trientine had an adverse effect of anemia. Four patients receiving trientine died during follow-up, 3 having shown initial neurologic deterioration. Neurologic and speech recovery during a 3-year follow-up period were quite good.Conclusion: Tetrathiomolybdate is a better choice than trientine for preserving neurologic function in patients who present with neurologic disease.