Centre de référence des maladies systémiques auto-immunes rares, département de médecine interne, hôpital Cochin, Assistance publique-Hôpitaux de Paris, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France; Université Paris Descartes, 12, rue de l'École-de-Médecine, 75006 Paris, France; Institut Cochin, Inserm U1016, CNRS UMR 8104, Paris, France.
Joint Bone Spine. 2019 May;86(3):321-326. doi: 10.1016/j.jbspin.2018.09.002. Epub 2018 Sep 7.
Targeted immunotherapy is substantially improving the management of ANCA-associated vasculitides (AAV), which include granulomatosis with polyangiitis (GPA, Wegener's granulomatosis), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). This article reviews the current role for targeted immunotherapy in AAV, its validated indications, and avenues for further development. Rituximab is a validated induction treatment for GPA and severe MPA. Rituximab in these indications is not less effective than cyclophosphamide and is particularly useful in patients with refractory or relapsing disease, women of childbearing potential, and patients previously treated with cyclophosphamide. Rituximab is more effective than cyclophosphamide for treating relapses. For remission maintenance therapy, which is indispensable, rituximab has been proven superior over conventional immunosuppressive treatment. Rituximab is licensed in the USA and in Europe for the induction treatment of severe forms of GPA and MPA. An extension study for remission maintenance therapy is ongoing. In EGPA, although maintenance treatment with the interleukin-5 antagonist mepolizumab is effective in decreasing glucocorticoid requirements and in alleviating asthma and sinonasal symptoms, its efficacy on the vasculitis remains somewhat unclear. Mepolizumab is licensed for use in EGPA, and rituximab is also being evaluated as an induction and maintenance agent. Immunoglobulins can be helpful as an adjuvant treatment for active AAV with severe immunedepression, notably when infections occur. Plasma exchange is indicated in AAV with advanced renal dysfunction and, perhaps, in the event of alveolar hemorrhage, a possibility that will be assessed in 2018 in a large international study.
靶向免疫疗法在很大程度上改善了抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（AAV）的治疗，其中包括肉芽肿性多血管炎（GPA，韦格纳肉芽肿）、显微镜下多血管炎（MPA）和嗜酸性肉芽肿性多血管炎（EGPA，Churg-Strauss 综合征）。本文综述了靶向免疫疗法在 AAV 中的当前作用、其已验证的适应证以及进一步发展的途径。利妥昔单抗是 GPA 和严重 MPA 的有效诱导治疗药物。在这些适应证中，利妥昔单抗与环磷酰胺一样有效，尤其适用于难治性或复发性疾病、有生育能力的女性以及既往接受过环磷酰胺治疗的患者。利妥昔单抗在治疗复发方面比环磷酰胺更有效。对于不可或缺的缓解维持治疗，利妥昔单抗已被证明优于常规免疫抑制治疗。利妥昔单抗已在美国和欧洲获得批准，用于严重 GPA 和 MPA 的诱导治疗。一项用于缓解维持治疗的扩展研究正在进行中。在 EGPA 中，尽管白细胞介素-5 拮抗剂美泊利珠单抗用于减少糖皮质激素需求和缓解哮喘和鼻旁窦症状的维持治疗有效，但它对血管炎的疗效仍有些不清楚。美泊利珠单抗已被批准用于 EGPA，利妥昔单抗也正在被评估为诱导和维持药物。免疫球蛋白可作为严重免疫抑制的活动性 AAV 的辅助治疗，尤其是在发生感染时。当出现晚期肾功能不全时，需要进行血浆置换，也许在肺泡出血时也需要进行血浆置换，这一可能性将在 2018 年的一项大型国际研究中进行评估。
