Petri Michelle, Brodsky Robert A, Jones Richard J, Gladstone Douglas, Fillius Michael, Magder Laurence S
Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Arthritis Rheum. 2010 May;62(5):1487-93. doi: 10.1002/art.27371.
Monthly intravenous (IV) cyclophosphamide for 6 months has been the standard induction regimen for lupus nephritis, followed by a maintenance regimen of quarterly infusions for 2 years. We undertook this study to compare the efficacy and safety of the standard regimen versus a high-dose IV cyclophosphamide regimen.
We performed a prospective randomized trial comparing monthly IV cyclophosphamide at 750 mg/m(2) body surface area for 6 months followed by quarterly IV cyclophosphamide for 2 years (traditional treatment) against high-dose IV cyclophosphamide (50 mg/kg daily for 4 days) (high-dose treatment). Entry criteria included renal lupus, neurologic lupus, or other organ system involvement with moderate-to-severe activity.
Fifty-one patients were randomized; 3 withdrew before treatment and 1 committed suicide after 2 months of high-dose treatment. Twenty-two had renal lupus, 14 had neurologic lupus, and 11 had other organ involvement. The outcome measure was the Responder Index for Lupus Erythematosus (complete response, partial response, no change, or worsening). At 6 months (the end of induction), 11 of 21 patients (52%) in the high-dose treatment group had a complete response compared with 9 of 26 patients (35%) in the traditional treatment group (P = 0.13). At the final visit (30 months), 10 of 21 patients (48%) in the high-dose treatment group had a complete response compared with 13 of 20 patients (65%) who continued with traditional treatment (P = 0.13). Six patients crossed over from traditional treatment to high-dose treatment because of lack of response, and 3 of those patients became complete responders.
There was not strong evidence that monthly IV cyclophosphamide and high-dose IV cyclophosphamide differed in complete or in any (complete or partial) response to induction or maintenance therapy. However, nonresponders to monthly IV cyclophosphamide can sometimes be rescued with high-dose IV cyclophosphamide.
每月静脉注射环磷酰胺6个月一直是狼疮性肾炎的标准诱导方案，随后是为期2年的每季度一次输注的维持方案。我们开展这项研究以比较标准方案与高剂量静脉注射环磷酰胺方案的疗效和安全性。
我们进行了一项前瞻性随机试验，将每月按体表面积750mg/m²静脉注射环磷酰胺6个月，随后每季度静脉注射环磷酰胺2年（传统治疗）与高剂量静脉注射环磷酰胺（每日50mg/kg，共4天）（高剂量治疗）进行比较。纳入标准包括肾性狼疮、神经精神性狼疮或其他伴有中度至重度活动的器官系统受累。
51例患者被随机分组；3例在治疗前退出，1例在高剂量治疗2个月后自杀。22例有肾性狼疮，14例有神经精神性狼疮，11例有其他器官受累。结局指标是红斑狼疮反应指数（完全缓解、部分缓解、无变化或恶化）。在6个月时（诱导期结束），高剂量治疗组21例患者中有11例（52%）完全缓解，而传统治疗组26例患者中有9例（35%）完全缓解（P = 0.13）。在最后一次随访时（30个月），高剂量治疗组21例患者中有10例（48%）完全缓解，而继续接受传统治疗的20例患者中有13例（65%）完全缓解（P = 0.13）。6例因无反应从传统治疗转至高剂量治疗的患者中，有3例成为完全缓解者。
没有强有力的证据表明每月静脉注射环磷酰胺与高剂量静脉注射环磷酰胺在诱导或维持治疗的完全缓解或任何（完全或部分）反应方面存在差异。然而，对每月静脉注射环磷酰胺无反应者有时可通过高剂量静脉注射环磷酰胺挽救。
