Lupus Research Unit, The Rayne Institute, St Thomas' Hospital, London SE1 7EH, UK.
Lupus. 2013 May;22(6):574-82. doi: 10.1177/0961203313483376. Epub 2013 Apr 30.
The objective of this paper is to report the clinical outcome of B cell depletion therapy in 18 patients with refractory lupus nephritis (LN).
Eighteen patients received rituximab on an open-label basis with prospective evaluations. All patients had renal disease refractory to conventional immunosuppressive therapy, including intravenous cyclophosphamide (CyC). All patients fulfilled the revised ACR classification criteria for SLE. Rituximab was given as 2 × 1 g infusions with 500 mg iv CyC and 500 mg iv methylprednisolone, two weeks apart. Complete remission (CR) of nephritis at six months was defined as normal serum creatinine and serum albumin levels, inactive urine sediment, and proteinuria < 0.5 g/day; partial remission (PR) was defined as a ≥50% improvement in all renal parameters that were abnormal at baseline. Clinical response was assessed by the British Isles Lupus Assessment Group (BILAG) score pre- and post-rituximab treatment, and efficacy was recorded by extent and duration of B lymphocyte depletion (normal range 0.100-0.500 × 10(9)/l). Follow-up data were collected at six months, one year post-treatment and at the most recent clinic visit.
At six months, 11/18 patients reached renal CR and two of 18 PR. The mean global BILAG scores for responders decreased from 15 (SD 10) to 5 (SD 3), and a total of ten A scores disappeared. Five patients failed to show complete or partial renal response despite peripheral B lymphocyte count depletion, and progressed to end-stage renal failure (ESRF) and dialysis. Four of these patients had severe proliferative, crescentic nephritis, of whom three had Class IV-G, one Class III and one late membranous glomerulonephritis. One patient died six years after rituximab therapy from overwhelming sepsis while on long-term haemodialysis.
Rituximab therapy achieved a response in 13/18 patients with refractory LN. However, in patients with rapidly progressive crescentic LN, when there is already evidence of significant renal impairment, rituximab therapy may not prevent progression to ESRF and dialysis. Our data also suggest that severe Class IV-G LN may be associated with a poor response to therapy.
本文旨在报告 18 例难治性狼疮肾炎（LN）患者接受 B 细胞耗竭治疗的临床结果。
18 例患者接受利妥昔单抗开放标签治疗，并进行前瞻性评估。所有患者均患有对常规免疫抑制治疗（包括静脉注射环磷酰胺[CyC]）无效的肾脏疾病。所有患者均符合修订后的 ACR 分类标准的 SLE 标准。利妥昔单抗以 2×1g 输注，每两周一次，每次给予 500mg iv CyC 和 500mg iv 甲基强的松龙。六个月时肾炎完全缓解（CR）定义为血清肌酐和血清白蛋白水平正常、尿沉渣无活动、蛋白尿<0.5g/天；部分缓解（PR）定义为所有基线异常的肾脏参数均改善≥50%。临床反应通过治疗前后不列颠群岛狼疮评估组（BILAG）评分评估，疗效通过 B 淋巴细胞耗竭的程度和持续时间（正常范围 0.100-0.500×10（9）/l）记录。收集治疗后 6 个月、1 年和最近的临床就诊时的随访数据。
在 6 个月时，18 例患者中有 11 例达到肾脏 CR，2 例达到 PR。应答者的平均全球 BILAG 评分从 15（SD 10）降至 5（SD 3），共 10 个 A 评分消失。尽管外周 B 淋巴细胞计数耗竭，但仍有 5 例患者未完全或部分出现肾脏反应，并进展为终末期肾衰竭（ESRF）和透析。其中 4 例患者有严重的增生性、新月体性肾炎，其中 3 例为 IV-G 级，1 例为 III 级，1 例为晚期膜性肾小球肾炎。1 例患者在利妥昔单抗治疗 6 年后死于长期血液透析时的败血症。
利妥昔单抗治疗在 18 例难治性 LN 患者中取得了应答。然而，在快速进展性新月体性 LN 患者中，当已经存在明显的肾功能损害证据时，利妥昔单抗治疗可能无法阻止进展为 ESRF 和透析。我们的数据还表明，严重的 IV-G 级 LN 可能与治疗反应不佳有关。
