Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Department of Medicine, St. Joseph's Regional Medical Centre, Paterson, USA.
Lupus. 2020 Jul;29(8):892-912. doi: 10.1177/0961203320928412. Epub 2020 Jun 2.
Rituximab (RTX) has important usage in rheumatoid arthritis and vasculitis. There remains a need for more, better, and safer treatments for patients with lupus nephritis (LN). RTX has been trialed in such patients without definitive conclusions about its effectiveness. As a role for RTX has not been clearly established for LN, we carried out a systematic review and analysis.
We identified 31 studies of RTX for class I-VI LN, and assessed complete renal response (CRR) and partial renal response (PRR) using criteria including serum creatinine, proteinuria, and urinary sediment. Due to differences in the pediatric presentation of the disease, studies focusing on pediatric patients were excluded.
One randomized controlled trial (RCT) showed superiority of RTX+cyclophosphamide (CYC) versus CYC alone (64% vs. 21% CRR and 19% vs. 36% PRR). Six prospective and retrospective studies utilizing RTX monotherapy found 66% CRR or PRR in all patients. Eleven studies that investigated RTX in combination with CYC or mycophenolate mofetil (MMF) also found 66% CRR or PRR in all patients. In total, the CRR for Caucasian, East Asian, and Hispanic patients were 77%, 38%, and 28%, respectively.
RTX appeared to benefit certain LN patients, but most studies were not randomized or properly controlled, were heterogeneous in design, subjects, and LN types, and were not comparable, and must therefore be interpreted cautiously. RTX alone may not deplete B cells sufficiently for the perturbations of LN. In addition, RTX may induce responses differently among patients of different ethnic and racial backgrounds. Furthermore, there were wide variations in the baseline characteristics of the patients, namely LN class, time course of disease, age, and prior immunosuppressive use. We suggest a prospective RCT in patients aged 18-65 years with class IV LN. Ideally, the patients would not have received prior immunosuppression and would better represent different ethnicities. The treatment groups would be RTX, RTX+belimumab, CYC, and MMF groups, with pulse-dose steroids during induction followed by maintenance steroids and MMF. The CRR and PRR would be assessed at 12 and 24 months. This or a similar study might clarify RTX's role in the treatment of LN.
利妥昔单抗（RTX）在类风湿关节炎和血管炎中具有重要作用。对于狼疮肾炎（LN）患者，仍需要更好、更安全的治疗方法。RTX 已在这类患者中进行了试验，但关于其疗效尚无明确结论。由于 RTX 在 LN 中的作用尚未明确，我们进行了系统评价和分析。
我们确定了 31 项 RTX 治疗 I-VI 级 LN 的研究，并根据血清肌酐、蛋白尿和尿沉渣等标准评估完全肾缓解（CRR）和部分肾缓解（PRR）。由于疾病在儿科表现的差异，排除了专门针对儿科患者的研究。
一项随机对照试验（RCT）显示 RTX+环磷酰胺（CYC）组优于 CYC 单药组（64% vs. 21%CRR 和 19% vs. 36%PRR）。六项前瞻性和回顾性研究使用 RTX 单药治疗，发现所有患者的 CRR 或 PRR 为 66%。11 项研究表明，RTX 联合 CYC 或霉酚酸酯（MMF）治疗所有患者的 CRR 或 PRR 也为 66%。总的来说，白种人、东亚人和西班牙裔患者的 CRR 分别为 77%、38%和 28%。
RTX 似乎对某些 LN 患者有益，但大多数研究未随机或未进行适当对照，设计、对象和 LN 类型存在异质性，且不可比，因此必须谨慎解释。RTX 单药治疗可能不足以耗尽 LN 中的 B 细胞。此外，RTX 可能会在不同种族和背景的患者中引起不同的反应。此外，患者的基线特征存在很大差异，即 LN 分级、疾病病程、年龄和既往免疫抑制治疗。我们建议在 18-65 岁的 IV 级 LN 患者中进行前瞻性 RCT。理想情况下，患者未接受过免疫抑制治疗，并且更好地代表不同的种族。治疗组将为 RTX、RTX+贝利木单抗、CYC 和 MMF 组，诱导期给予脉冲剂量类固醇，随后给予维持剂量类固醇和 MMF。在 12 个月和 24 个月时评估 CRR 和 PRR。该研究或类似研究可能会阐明 RTX 在 LN 治疗中的作用。
