肾脏病学中单剂低剂量利妥昔单抗的临床应答和 B 细胞抑制模式。
Clinical Response and Pattern of B cell Suppression with Single Low Dose Rituximab in Nephrology.
机构信息
Department of Nephrology, Government Medical College Thiruvananthapuram, Thiruvananthapuram, Kerala, India.
出版信息
Kidney360. 2020 Apr 2;1(5):359-367. doi: 10.34067/KID.0000072020. eCollection 2020 May 28.
BACKGROUND
There is no consensus regarding dose and frequency of rituximab in nephrology with extrapolation of doses used in treating lymphoproliferative disorders. There are no guidelines on targeting initial and subsequent doses on the basis of CD19 B cells.
METHODS
Initially, 100 mg rituximab was given to 42 adults with steroid-dependent nephrotic syndrome (SDNS) and frequently relapsing nephrotic syndrome (FRNS), idiopathic membranous nephropathy (MN), and high-immunologic-risk kidney transplantation. Absolute and percentage levels of CD19 B cells and clinical status were assessed at baseline, days 30, 90, and 180, and at 1 year. Subsequent doses of rituximab were on the basis of CD19 B cell reconstitution and clinical response.
RESULTS
CD19 B cell percentage decreased from 16.3 ± 7.6 to 0.3 ± 0.3 (≤0.001), 1.9 ± 1.7 (≤0.001), and 4.0 ± 4.5 (=0.005) by 30, 90, and 180 days, respectively. Suppression of CD19 B cell count below 1% at days 30, 90, and 180 was seen in 40 of 42 (95.2%), 18 of 42 (42.9%), and 7 of 42 (16.7%) patients, respectively. Of 30 with SDNS and FRNS followed up for 1 year, 29 (96.7%) went into remission at day 30. Remission was sustained in 23 (76.6%) at day 180 and 21 (70%) at 1 year. There was a significant decrease (<0.001) in the dose of steroids needed to maintain remission at 180 days after rituximab (0.27 ± 0.02 mg/kg to 0.02 ± 0.00 mg/kg). CD19 B cell percentage at 90 days correlated with relapse (=0.001; odds ratio 1.42; 95% confidence interval, 1.25 to 2.57). Eighteen (60%) required an additional dose. Of five with MN, four achieved remission by 6 months, which was sustained in three by 1 year. Of the seven kidney transplant recipients, two had antibody-mediated rejections, although CD19 B cells were suppressed even at 1 year.
CONCLUSIONS
Low-dose rituximab induces sustained depletion of CD19 B cells for up to 90 days. Its role in preventing relapses in SDNS, FRNS, MN, and rejection needs further study.
背景
在肾脏病学中，利妥昔单抗的剂量和频率尚无共识，其剂量是从治疗淋巴增生性疾病中推断出来的。目前尚无基于 CD19 B 细胞针对初始和后续剂量的指南。
方法
最初，给 42 例患有激素依赖性肾病综合征（SDNS）和频繁复发肾病综合征（FRNS）、特发性膜性肾病（MN）和高免疫风险肾移植的成人患者使用 100mg 利妥昔单抗。在基线、第 30、90 和 180 天以及第 1 年评估绝对和百分比 CD19 B 细胞水平和临床状态。根据 CD19 B 细胞重建和临床反应确定后续利妥昔单抗剂量。
结果
CD19 B 细胞百分比从 16.3±7.6 降至 0.3±0.3（≤0.001）、1.9±1.7（≤0.001）和 4.0±4.5（=0.005），分别在第 30、90 和 180 天达到。第 30、90 和 180 天，42 例患者中有 40 例（95.2%）、18 例（42.9%）和 7 例（16.7%）的 CD19 B 细胞计数降至 1%以下。在接受 SDNS 和 FRNS 治疗的 30 例患者中，有 29 例（96.7%）在第 30 天缓解。第 180 天有 23 例（76.6%）和第 1 年有 21 例（70%）缓解持续。在第 180 天时，需要维持缓解的皮质类固醇剂量显著降低（利妥昔单抗治疗后 0.27±0.02mg/kg 至 0.02±0.00mg/kg，<0.001）。第 90 天的 CD19 B 细胞百分比与复发相关（=0.001；优势比 1.42；95%置信区间，1.25 至 2.57）。18 例（60%）需要额外剂量。5 例 MN 患者中，4 例在 6 个月时缓解，其中 3 例缓解持续至 1 年。7 例肾移植受者中，有 2 例发生抗体介导的排斥反应，尽管在 1 年内 CD19 B 细胞仍受到抑制。
结论
低剂量利妥昔单抗可诱导 CD19 B 细胞持续耗竭长达 90 天。其在预防 SDNS、FRNS、MN 和排斥反应中的作用需要进一步研究。
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