Cravedi Paolo, Ruggenenti Piero, Sghirlanzoni Maria Chiara, Remuzzi Giuseppe
Clinical Research Centre for Rare Diseases Aldo e Cele Daccò, Mario Negri Institute for Pharmacological Research, Villa Camozzi, Ranica, Italy.
Clin J Am Soc Nephrol. 2007 Sep;2(5):932-7. doi: 10.2215/CJN.01180307. Epub 2007 Aug 16.
Rituximab, given in four weekly doses, is a promising treatment for idiopathic membranous nephropathy and other immune-mediated diseases and lymphoproliferative disorders. This multidose regimen, however, may cause hypersensitivity reactions and is extremely expensive. This study was aimed at evaluating whether titrating rituximab to circulating CD20 B cells may improve safety and limit costs of treatment.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a matched-cohort, single-center, controlled study, the outcome of 12 new incident patients who had idiopathic membranous nephropathy and nephrotic syndrome and received a B cell-driven treatment was compared with that of 24 historical reference patients who were given the standard protocol of four weekly doses of 375 mg/m2.
Only one patient needed a second dose to achieve full CD20 cell depletion. At 1 yr, time course of the components of nephrotic syndrome and the proportion of patients who achieved disease remission (25%) was identical in both groups. Persistent CD20 cell depletion was achieved in all patients. Costs for rituximab treatment and hospitalizations totalled 3770.90 euros ($4902.20) and 13,977.60 euros ($18,170.80) with the B cell-driven and the four-dose protocol, respectively. One patient on standard protocol had a severe adverse reaction at second rituximab dose. Thus, B cell titrated as effectively as standard rituximab treatment achieves B cell depletion and idiopathic membranous nephropathy remission but is fourfold less expensive, allowing for more than 10,000 euros, approximately $13,000 in savings per patient.
Avoiding unnecessary reexposure to rituximab is extremely cost-saving and may limit the production of antichimeric antibodies that may increase the risk for adverse reactions and prevent re-treatment of disease recurrences.
利妥昔单抗,每周给药一次,共四次,是一种治疗特发性膜性肾病及其他免疫介导疾病和淋巴增殖性疾病的有前景的疗法。然而,这种多剂量方案可能会引起过敏反应,且费用极高。本研究旨在评估根据循环CD20 B细胞滴定利妥昔单抗是否可提高安全性并降低治疗成本。
设计、地点、参与者及测量指标:在一项匹配队列、单中心、对照研究中,将12例新诊断的患有特发性膜性肾病和肾病综合征并接受B细胞驱动治疗的患者的治疗结果,与24例接受每周一次、共四次、每次375mg/m²标准方案治疗的历史对照患者的结果进行比较。
仅1例患者需要第二次给药以实现完全的CD20细胞清除。在1年时,两组肾病综合征各组分的时间进程以及疾病缓解患者的比例(25%)相同。所有患者均实现了持续的CD20细胞清除。采用B细胞驱动方案和四剂量方案时,利妥昔单抗治疗及住院的费用分别总计3770.90欧元(4902.20美元)和13977.60欧元(18170.80美元)。接受标准方案治疗的1例患者在第二次使用利妥昔单抗时出现严重不良反应。因此,根据B细胞滴定的利妥昔单抗与标准利妥昔单抗治疗一样有效地实现了B细胞清除和特发性膜性肾病缓解,但费用降低了四倍,每位患者可节省超过10000欧元,约合13000美元。
避免不必要的利妥昔单抗再次暴露极具成本效益,且可能限制抗嵌合抗体的产生,而这种抗体会增加不良反应风险并阻碍疾病复发时的再次治疗。