University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX, 75390, USA.
Texas Scottish Rite Hospital, Dallas, TX, USA.
Pediatr Nephrol. 2019 Nov;34(11):2295-2309. doi: 10.1007/s00467-018-4076-2. Epub 2018 Sep 10.
Recent advances have allowed better understanding of vasculitis pathogenesis and led to more targeted therapies. Two pivotal randomized controlled trials, RITUXVAS and rituximab in ANCA-associated vasculitis (RAVE), provide high-quality evidence demonstrating rituximab (RTX) is efficacious in inducing remission in adult ANCA-associated vasculitis (AAV) patients compared with cyclophosphamide (CYC). RAVE also demonstrated superiority of RTX to oral CYC for induction of remission in relapsing disease. Disappointingly, the RTX regimen was not associated with reduction in early serious adverse events. At least nine randomized trials are in progress, aiming to further delineate optimal dosing and duration of RTX therapy in AAV. In particular, the 6-month interim results of the PEPRS trial provide encouraging data specific to children. Due to special concerns related to growth, preservation of fertility, and potential for high cumulative medication doses, children with AAV should be considered as candidates for RTX even as a first-line remission induction therapy. Two randomized clinical trials have defined the role of infliximab in Kawasaki disease (KD), which appears to be as an alternative to a second infusion of intravenous immunoglobulin (IVIG) for treatment-resistant disease. Support for other biologics in the treatment of AAV or for biologics in the treatment of other vasculidities is largely lacking due to either unimpressive trial results or lack of trials. Except for the KD trials and the PEPRS, trials enrolling children remain scant. This review touches on the key trials and case series with biologics in the treatment of vasculitis that have influenced practice and shaped current thinking.
近年来，研究进展使人们更好地了解了血管炎的发病机制，并促成了更具针对性的治疗方法。两项关键性的随机对照试验，即 RITUXVAS 试验和抗中性粒细胞胞质抗体相关性血管炎（AAV）中的利妥昔单抗（RTX）试验，提供了高质量的证据，表明与环磷酰胺（CYC）相比，RTX 可有效诱导成人 AAV 患者缓解。RAVE 试验还表明，RTX 诱导缓解复发性疾病的疗效优于口服 CYC。令人失望的是，RTX 方案并未降低早期严重不良事件的发生率。目前至少有 9 项随机试验正在进行中，旨在进一步明确 AAV 患者 RTX 治疗的最佳剂量和疗程。特别是，PEPRS 试验的 6 个月中期结果提供了针对儿童的令人鼓舞的数据。由于与生长、生育力保护和潜在的高累积药物剂量相关的特殊问题，儿童 AAV 患者应被视为 RTX 的候选者，即使作为一线缓解诱导治疗。两项随机临床试验确定了英夫利昔单抗在川崎病（KD）中的作用，它似乎可以替代治疗抵抗性疾病的第二剂静脉注射免疫球蛋白（IVIG）。由于试验结果不佳或缺乏试验，其他生物制剂在 AAV 治疗中的作用或生物制剂在其他血管炎治疗中的作用的支持证据很少。除 KD 试验和 PEPRS 外，招募儿童的试验仍然很少。本综述涉及到在血管炎治疗中使用生物制剂的关键试验和病例系列，这些试验和病例系列影响了临床实践并塑造了当前的治疗思路。
