CASE SERIES OF PATIENTS UNDER BIWEEKLY TREATMENT WITH LARONIDASE: A REPORT OF A SINGLE CENTER EXPERIENCE

ABSTRACT Objective: To report the stabilization of urinary glycosaminoglicans (GAG) excretion and clinical improvements in patients with mucopolysaccharidosis type I (MPS I) under an alternative dose regimen of laronidase of 1.2 mg/kg every other week. Methods: We participated in a dose-optimization trial for laronidase in MPS-I patients using four alternative regimens: 0.58 mg/kg every week, 1.2 mg/kg every two weeks, 1.2 mg/kg every week and 1.8 mg/kg every other week (EOW). After the trial ended, the patients resumed the recommended dose and regimen of 0.58 mg/kg every week. Under this regimen, some patients presented difficulties in venous access and were unable to commute weekly to the treatment center. Therefore, we used an alternative regimen that consisted of 1.2 mg/kg EOW in eight patients. A retrospective study of medical records of MPS-I patients who underwent both enzyme replacement therapy (ERT) regimens, of 0.58 mg/kg every week and 1.2 mg/kg EOW, was done. Results: Patients remained clinically stable under the alternative regimen, did not present elevation of urinary GAG nor any adverse event. Conclusions: The switch of dose regimen to 1.2 mg/kg EOW of laronidase was safe, and did not cause any clinical worsening in patients who had been previously under standard dose ERT.摘要 研究目的：本研究旨在报告采用每两周1.2 mg/kg的拉罗尼酶（laronidase）替代给药方案治疗的Ⅰ型黏多糖贮积症（mucopolysaccharidosis type I, MPS I）患者的尿糖胺聚糖（glycosaminoglicans, GAG）排泄稳定性及临床转归改善情况。 研究方法：本研究参与了一项针对MPS-I患者拉罗尼酶的剂量优化试验，共设置4种替代给药方案：每周0.58 mg/kg、每两周1.2 mg/kg、每周1.2 mg/kg以及每两周1.8 mg/kg。试验结束后，患者恢复标准推荐给药方案：每周0.58 mg/kg。部分采用该标准方案的患者存在静脉通路困难，且无法每周往返治疗中心，因此对8例患者采用了每两周1.2 mg/kg的替代给药方案。本研究对同时接受过两种酶替代疗法（enzyme replacement therapy, ERT）方案（每周0.58 mg/kg与每两周1.2 mg/kg）的MPS-I患者的病历进行了回顾性分析。 研究结果：采用该替代给药方案的患者临床状态保持稳定，未出现尿GAG水平升高，亦未发生任何不良事件。 研究结论：将拉罗尼酶给药方案调整为每两周1.2 mg/kg具有安全性，未对此前接受标准剂量酶替代疗法的患者造成临床病情恶化。