超小剂量利妥昔单抗治疗狼疮性肾炎的临床观察研究

Ultra-low dose rituximab regimen for treatment of lupus nephritis:an observational study

目的:探讨超小剂量利妥昔单抗(RTX)方案治疗狼疮性肾炎(LN)的疗效及安全性。方法:34例LN接受超小剂量RTX(RTX 100 mg/周×4周后改为RTX 100 mg每2~3个月一次)并联合免疫抑制剂治疗。B细胞耗竭和B细胞完全耗竭分别定义为CD19^(+)细胞<5个/μL和CD19^(+)细胞<1个/μL,B细胞重建定义为CD19^(+)细胞≥5个/μL。分析超小剂量方案治疗LN 12月的疗效和不良反应。结果:34例LN中19例为难治性LN,8例为复发LN,7例为初发LN。治疗前11例表现为肾病综合征,8例合并急性肾损伤(AKI),7例合并严重自身免疫性溶血性贫血和(或)免疫性血小板减低。RTX 100 mg/周×4周时33例(97.1%)达到B细胞完全耗竭,12月内持续B细胞耗竭及完全耗竭的比例分别为67.6%和52.9%。12月内累积32例(94.1%)患者获得肾脏缓解,其中12例(35.5%)获得肾脏完全缓解,7例免疫性血细胞减少患者血细胞均升至正常。RTX治疗后第6个月、第9个月、第12个月肾脏缓解率分别为82.4%、88.2%及91.1%,初发、复发及难治性LN患者的肾脏缓解率无差异(分别为85.7%、100%、94.7%),初发LN的完全肾脏缓解率显著高于难治性LN(71.4%vs 21.1%,P=0.024)。12月内11例患者B细胞重建,其中2例LN复发。3例并发感染,无一例死亡。结论:超小剂量RTX联合免疫抑制剂对顽固、复发和初发LN均显示很高的临床缓解率,值得进一步临床随机对照研究。

Objective:In this study,we investigate the clinical efficacy and safety of ultra-low dose Rituximab(RTX)regimen for treatment of lupus nephritis(LN).Methodology:34 Patients with renal biopsy-proven LN were treated with ultra-low dose RTX regimen(RTX 100 mg/w×4 w followed by RTX 100 mg every 2~3 months for 12 months)in combination with glucocorticoids and immunosuppressive agents.B cell depletion and B cell complete depletion were defined as CD19^(+)cells<5/μL and CD19^(+)cells<1/μL respectively,and B cell reconstruction was defined as CD19^(+)cells≥5/μL.Clinical efficacy and adverse events were retrospectively analyzed within 12 months.Results:Thirty-four LN patients including 19 refractory,8 relapsed and 7 new onset LN were included in this study.Before RTX treatment,11 patients showed nephrotic syndrome,8 patients had acute renal injury(AKI)and 7 patients also presented with severe immune cytopenia.In addition to RTX,all patients received immunosuppressant including calcineurin inhibitors(n=30)or mycophenolate mofetil(n=4).After four ultra-low dose RTX treatment,33 patients(97.1%)achieved B cell complete depletion.23(67.6%)and 18(52.9%)patients showed sustained B cell depletion and B cell complete depletion within 12 months of RTX treatment.Totally,32 patients(94.1%)achieved remission and 12(35.3%)achieved complete remission.No significant difference in remission rates was found among refractory LN(94.7%),relapsed LN(100%)and new onset LN(85.7%),but complete remission rate was significantly higher in new onset LN patients than that in refractory LN(71.4%vs 21.4%,P=0.024).Renal function was recovered in 7(87.5%)patients with AKI on admission.All seven patients accompanied with immune cytopenia achieved normalization of blood cell account.ANA and Anti-ds-DNA tigers turned to negative in 3(8.8%)and 13(86.7%)patients respectively.B cells reconstituted in 11 patients,2 of whom experienced LN relapse.Infection occurred in 3 patients within the first 3 months,no patient died.Conclusion:Ultra-Low dose RTX regimen for lupus nephritis showed a promising efficiency,especially for new onset patients.It is worth carrying out a prospective controlled study of ultra-low dose RTX regimen in treatment of LN.