Lupus nephritis (LN) is a severe consequence of systemic lupus erythematosus (SLE) that affects approximately 40% of patients. Pathogenic immune complexes that are characteristic of LN deposit in the kidney and activate immune mediated pathways including the complement system. Complete remission rates in LN are approximately 44% highlighting the need for new treatment strategies in these patients. Eculizumab is a fully humanised IgG2/IgG4 monoclonal antibody directed at C5 and thus prevents the formation of the terminal complement complex. Eculizumab is successfully used in atypical haemolytic uraemic syndrome (aHUS) and paroxysomal nocturnal haemoglobinuria (PNH) but it is not standardly used in LN. The aim of this project was to determine whether there is any role for eculizumab as adjunctive therapy in LN. Using a predefined search strategy on Ovid MEDLINE and EMBASE the literature was reviewed systematically to identify studies in which eculizumab had been used to treat patients with SLE. All patients were included that were treated with complement inhibitors. Favourable outcome in this study was defined as resolution of symptoms that led to treatment, discharge from hospital or recovery of renal function. Patients were excluded if there was no outcome data or if complement inhibition was unrelated to their SLE. From 192 abstracts screened, 14 articles were identified, involving 30 patients. All SLE patients administered eculizumab were treated for thrombotic microangiopathy (TMA) secondary to LN diagnosed either histologically (66%) or as part of a diagnosis of aHUS (73%). 93% of patients had a favourable outcome in response to eculizumab treatment, of which 46% had a favourable outcome and successfully stopped treatment without relapse in symptoms during a median follow up of 7 months. Three patients (10%) reported adverse outcomes related to eculizumab therapy. Scientific evidence supports the involvement of complement in the pathogenesis of LN however the role of complement inhibition in clinical practice is limited to those with TMA features. This systematic review showed that in cases of LN complicated with TMA, eculizumab seems to be a very efficacious therapy. Further evidence is required to determine whether patients with refractory LN may benefit from adjunctive complement inhibition.

中文翻译：

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系统评价依库珠单抗在系统性红斑狼疮相关血栓性微血管病中的作用。

狼疮性肾炎 (LN) 是系统性红斑狼疮 (SLE) 的严重后果，影响约 40% 的患者。以 LN 沉积为特征的致病性免疫复合物在肾脏中沉积并激活免疫介导的途径，包括补体系统。LN 的完全缓解率约为 44%，这突出表明这些患者需要新的治疗策略。依库珠单抗是针对 C5 的完全人源化 IgG2/IgG4 单克隆抗体，因此可防止形成末端补体复合物。Eculizumab 已成功用于非典型溶血性尿毒症综合征 (aHUS) 和阵发性睡眠性血红蛋白尿 (PNH)，但未标准用于 LN。该项目的目的是确定依库珠单抗作为 LN 的辅助治疗是否有任何作用。使用 Ovid MEDLINE 和 EMBASE 上的预定义搜索策略，系统地审查了文献，以确定使用依库珠单抗治疗 SLE 患者的研究。包括所有接受补体抑制剂治疗的患者。本研究中的有利结果被定义为导致治疗、出院或肾功能恢复的症状消退。如果没有结果数据或补体抑制与其 SLE 无关，则排除患者。从筛选的 192 篇摘要中，确定了 14 篇文章，涉及 30 名患者。接受依库珠单抗治疗的所有 SLE 患者均接受了继发于组织学诊断 (66%) 或作为 aHUS 诊断 (73%) 诊断的 LN 继发的血栓性微血管病 (TMA) 的治疗。93% 的患者对依库珠单抗治疗有良好的结果，其中 46% 的患者有良好的结果并在中位随访 7 个月期间成功停止治疗且症状没有复发。三名患者 (10%) 报告了与依库珠单抗治疗相关的不良结果。科学证据支持补体参与 LN 的发病机制，但补体抑制在临床实践中的作用仅限于具有 TMA 特征的那些。该系统评价表明，在 LN 合并 TMA 的情况下，依库珠单抗似乎是一种非常有效的治疗方法。需要进一步的证据来确定难治性 LN 患者是否可以从辅助补体抑制中获益。其中 46% 有良好的结果并在中位随访 7 个月期间成功停止治疗且症状没有复发。三名患者 (10%) 报告了与依库珠单抗治疗相关的不良结果。科学证据支持补体参与 LN 的发病机制，但补体抑制在临床实践中的作用仅限于具有 TMA 特征的那些。该系统评价表明，在 LN 合并 TMA 的情况下，依库珠单抗似乎是一种非常有效的治疗方法。需要进一步的证据来确定难治性 LN 患者是否可以从辅助补体抑制中获益。其中 46% 有良好的结果并在中位随访 7 个月期间成功停止治疗且症状没有复发。三名患者 (10%) 报告了与依库珠单抗治疗相关的不良结果。科学证据支持补体参与 LN 的发病机制，但补体抑制在临床实践中的作用仅限于具有 TMA 特征的那些。该系统评价表明，在 LN 合并 TMA 的情况下，依库珠单抗似乎是一种非常有效的治疗方法。需要进一步的证据来确定难治性 LN 患者是否可以从辅助补体抑制中获益。科学证据支持补体参与 LN 的发病机制，但补体抑制在临床实践中的作用仅限于具有 TMA 特征的那些。该系统评价表明，在 LN 合并 TMA 的情况下，依库珠单抗似乎是一种非常有效的治疗方法。需要进一步的证据来确定难治性 LN 患者是否可以从辅助补体抑制中获益。科学证据支持补体参与 LN 的发病机制，但补体抑制在临床实践中的作用仅限于具有 TMA 特征的那些。该系统评价表明，在 LN 合并 TMA 的情况下，依库珠单抗似乎是一种非常有效的治疗方法。需要进一步的证据来确定难治性 LN 患者是否可以从辅助补体抑制中获益。