Puéchal Xavier, Guillevin Loïc
National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (APHP) centre, Université Paris Cité, Paris, France.
French Vasculitis Study Group, Hôpital Cochin, Paris, France.
Expert Rev Clin Immunol. 2022 Nov;18(11):1135-1143. doi: 10.1080/1744666X.2022.2122954. Epub 2022 Sep 14.
A two-stage therapeutic approach is now applied as standard-of-care to treat antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAVs): first, glucocorticoids (GCs) combined with cyclophosphamide (CYC) or rituximab (RTX) to induce remission, and then relapse prevention with remission-maintenance therapy. Nonetheless, a substantial risk of relapse persists.
The authors provide an overview of the current state of AAV remission-induction after relapse and maintenance therapies, and discuss new strategies recommended to prevent and treat relapses, focusing on granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).
For remission-induction after GPA or MPA relapse with organ-threatening manifestations, reintroduction or intensification of GCs in combination with CYC or RTX cycle is recommended; we prefer RTX in light of its superior responses obtained in patients with relapsing disease. Rapid tapering of GCs has been shown not to alter AAV evolution while decreasing the risk of serious infections. In contrast, for non-severe, active MPA, we recommend GCs alone as first-line therapy. For patients whose MPA remains uncontrolled by GCs alone, immunosuppressant adjunction can be a GC-sparing option or to counter GC intolerance. Once remission is achieved, we recommend prolonged maintenance therapy with preemptive low-dose (500 mg) RTX infusion biannually.
目前，两阶段治疗方法已作为治疗抗中性粒细胞胞浆抗体（ANCA）相关血管炎（AAV）的标准治疗方案应用：首先，使用糖皮质激素（GCs）联合环磷酰胺（CYC）或利妥昔单抗（RTX）诱导缓解，然后通过缓解维持治疗预防复发。尽管如此，复发风险仍然很大。
作者概述了AAV复发后诱导缓解和维持治疗的现状，并讨论了推荐用于预防和治疗复发的新策略，重点关注肉芽肿性多血管炎（GPA）和显微镜下多血管炎（MPA）。
对于伴有器官威胁表现的GPA或MPA复发后的诱导缓解，建议重新引入或强化GCs联合CYC或RTX周期治疗；鉴于复发疾病患者使用RTX获得的更好反应，我们更倾向于使用RTX。已表明快速减量GCs不会改变AAV的病程，同时可降低严重感染的风险。相比之下，对于非严重、活动性MPA，我们建议单独使用GCs作为一线治疗。对于仅使用GCs无法控制MPA的患者，加用免疫抑制剂可以作为减少GCs用量的选择或应对GCs不耐受的情况。一旦实现缓解，我们建议每半年进行一次低剂量（500 mg）RTX输注的长期维持治疗。
