Division of Hematology & Medical Oncology, Department of Medicine, Weill Cornell Medical College, New York, New York.
New York-Presbyterian Hospital, New York, New York.
Clin Adv Hematol Oncol. 2020 Apr;18(4):221-230.
Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) that is driven by uncontrolled activation of the alternative complement pathway, classically in the context of a genetic or autoimmune complement abnormality. Initial guidelines suggested lifelong treatment with the C5 inhibitor eculizumab, which until recently was the only therapy approved by the US Food and Drug Administration and European Medicines Agency for aHUS. However, multicenter observational studies provide compelling evidence that discontinuation of eculizumab, with careful monitoring for recurrence of renal injury, is an option for some patients. Although relapse occurs in 20% to 35% of patients with aHUS after a median of 3 months (range, 1-30 months) following eculizumab cessation, ostensibly irrespective of initial treatment duration, successful rescue with reinstitution of drug has been described in small cohorts if relapse is promptly recognized and eculizumab is immediately re-started. Rates of off-treatment TMA are higher in children than in adults; they are also elevated in those with a personal or family history of aHUS, certain complement mutations or anti-complement factor H autoantibodies, a renal allograft, or extrarenal manifestations of aHUS. Given the complex and unpredictable nature of aHUS, prospective trials defining the optimal treatment duration in diverse settings are required. In the interim, this review-which excludes pediatric patients and hematopoietic stem cell transplant recipients-suggests that eculizumab may be discontinued in some groups of patients; discontinuation should be undertaken on a case-by-case basis and with careful monitoring, following 6 to 12 months of treatment for aHUS that encompasses at least 3 months of normalization of renal function or stabilization of chronic renal disease.
非典型溶血性尿毒症综合征（aHUS）是一种由补体替代途径失控激活引起的血栓性微血管病（TMA），经典情况下与遗传或自身免疫性补体异常有关。最初的指南建议使用 C5 抑制剂依库珠单抗进行终身治疗，依库珠单抗直到最近才是唯一经美国食品和药物管理局（FDA）和欧洲药品管理局（EMA）批准用于治疗 aHUS 的药物。然而，多中心观察性研究提供了令人信服的证据，表明在仔细监测肾功能损伤复发的情况下，停止依库珠单抗治疗是一些患者的一种选择。尽管停止依库珠单抗治疗后，约 20%至 35%的 aHUS 患者在中位数为 3 个月（范围为 1-30 个月）后会复发，但复发显然与初始治疗持续时间无关，如果及时发现复发并立即重新开始使用依库珠单抗，在小队列中已成功挽救了患者。与成人相比，儿童停药后 TMA 的发生率更高；在有 aHUS 个人或家族史、某些补体突变或抗补体因子 H 自身抗体、肾移植或 aHUS 肾外表现的患者中，复发率也较高。鉴于 aHUS 的复杂和不可预测性质，需要进行前瞻性试验来确定在不同情况下的最佳治疗持续时间。在此期间，本综述（不包括儿科患者和造血干细胞移植受者）表明，依库珠单抗可能可以在某些患者群体中停止使用；在停止治疗前，应根据具体情况并在仔细监测下进行，停止治疗前，患者需要接受至少 3 个月的治疗，以确保肾功能正常或慢性肾病稳定。
