Rheumatology Department, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pz.le Golgi 2, 27100, Pavia, Italy.
PhD in Experimental Medicine, University of Pavia, Pavia, Italy.
Curr Rheumatol Rep. 2021 Apr 28;23(6):38. doi: 10.1007/s11926-021-01010-0.
The purpose of this review is to discuss the most recent evidence on the treatment innovations and future prospective in the management of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs).
In AAV, a growing body of research is available on novel treatment options for remission induction and to clarify some uncertainties concerning the optimal use of available drugs. Efforts are being made to reduce the toxicity associated with high-dose, prolonged glucocorticoids (GC) regimens. Despite major advances in the prognosis of AAV, relapses are still common and the intensity and duration of remission treatment constitute a great challenge in the management of these chronic conditions. A paradigm shift in practice in the management of AAV is being supported by recent evidence suggesting the comparable efficacy and improved safety profile of schemes with a reduced dose of GC for the induction and maintenance of remission in patients with severe granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Moreover, recent appraisal of pathogenetic mechanisms, including complement activation pathways, has introduced the revolutionary concept of an alternative to GC, such as avacopan. Plasma exchange failed to prevent end-stage renal disease and mortality in patients with severe renal involvement or pulmonary haemorrhage according to a large multicentre randomised trial. Intensified immunosuppressive strategies for patients with life-threatening manifestations, including the combination of rituximab (RTX) with cyclophosphamide (CYC) have revealed promising preliminary data. New evidence for the use of alternative immunosuppressive agents (e.g. mycophenolate mofetil or abatacept) for the induction of remission in patients with non-severe disease is emerging. Several studies have been recently published, or are ongoing, to assess the optimal strategy and duration of maintenance of remission with the available treatment options (GC, azathioprine, and RTX). Preliminary evidence supports the superiority of a more prolonged course of maintenance treatment. The management of refractory or relapsing eosinophilic granulomatosis with polyangiitis (EGPA) has been improved by the recent demonstration of efficacy and safety of an interleukin-5 inhibitor, mepolizumab. Ongoing randomised studies will clarify the role of RTX in patients with severe manifestations of EGPA.
本文旨在讨论抗中性粒细胞胞质抗体（ANCA）相关性血管炎（AAV）治疗创新和未来前景的最新证据。
在 AAV 中，关于新型治疗方案的研究越来越多，这些方案可用于诱导缓解，并澄清一些关于最佳使用现有药物的不确定性。目前正在努力降低与大剂量、长期糖皮质激素（GC）治疗方案相关的毒性。尽管 AAV 的预后有了很大的提高，但复发仍然很常见，缓解治疗的强度和持续时间在这些慢性疾病的管理中构成了巨大的挑战。近期的证据表明，对于严重肉芽肿性多血管炎（GPA）或显微镜下多血管炎（MPA）患者，GC 剂量减少的方案在诱导和维持缓解方面具有相似的疗效和改善的安全性，这一证据支持 AAV 管理实践的范式转变。此外，最近对发病机制的评估，包括补体激活途径，引入了替代 GC 的革命性概念，如 avacopan。根据一项大型多中心随机试验，血浆置换未能预防严重肾受累或肺出血患者的终末期肾病和死亡率。对于有生命威胁表现的患者，包括利妥昔单抗（RTX）联合环磷酰胺（CYC）的强化免疫抑制策略，已显示出有希望的初步数据。对于非严重疾病患者，使用替代免疫抑制剂（如霉酚酸酯或阿巴西普）诱导缓解的新证据正在出现。最近发表了几项研究，或正在进行中，以评估现有治疗方案（GC、硫唑嘌呤和 RTX）维持缓解的最佳策略和持续时间。初步证据支持更长期维持治疗的优越性。白细胞介素-5 抑制剂美泊利单抗的疗效和安全性的最近证实，改善了难治性或复发性嗜酸粒细胞性肉芽肿性多血管炎（EGPA）的治疗。正在进行的随机研究将阐明 RTX 在严重 EGPA 患者中的作用。
