Daratumumab for the treatment of refractory ANCA-associated vasculitis.
Daratumumab for the treatment of refractory ANCA-associated vasculitis.
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DOI：
10.1136/rmdopen-2022-002742
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发表时间：
2023-01
期刊：
影响因子：
6.2
通讯作者：
Schreiber A
中科院分区：
文献类型：
--
作者：
Ostendorf L;Burns M;Wagner DL;Enghard P;Amann K;Mei H;Eckardt KU;Seelow E;Schreiber A
目的难治性抗神经元胞质抗体（ANCA）相关性血管炎（AAV）是一种危及生命的疾病，目前尚无循证治疗方案。几种抗体介导的自身免疫性疾病的一种新兴治疗选择是抗CD 38抗体达雷妥尤单抗，其消耗分泌自身抗体的浆细胞。方法我们治疗了2例严重危及生命的AAV患者，尽管接受了利妥昔单抗和环磷酰胺诱导治疗，但仍有肾脏和肺部表现，其中4至8剂达雷妥尤单抗。我们跟踪了临床和免疫学反应。结果第一例髓过氧化物酶-ANCA阳性显微镜下多血管炎患者在达雷妥尤单抗治疗后，肺炎和胸膜炎消退，肾功能稳定。第2例患者患有蛋白酶3-ANCA阳性肉芽肿伴多血管炎、需要体外膜肺氧合（ECMO）的弥漫性肺泡出血和需要肾脏替代治疗的急性肾衰竭，在达雷妥尤单抗治疗后停用ECMO、机械通气和透析，出院回家。血清ANCA水平以及总IgG的大幅降低证实了临床改善，表明浆细胞耗竭。除CD 38+自然杀伤细胞耗竭外，血液白细胞水平未受到达雷妥尤单抗的显著影响。仅发生轻度不良事件，如低丙种球蛋白血症和上呼吸道感染。结论达雷妥尤单抗可安全有效地诱导2例重度难治性AAV患者缓解，可通过前瞻性临床试验确定其安全性和有效性。
Objective Treatment-refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a life-threatening condition without evidence-based treatment options. One emerging treatment option for several antibody-mediated autoimmune diseases is the anti-CD38 antibody daratumumab, which depletes autoantibody-secreting plasma cells. Methods We treated two patients with severe life-threatening AAV with renal and pulmonary manifestation despite induction therapy with rituximab and cyclophosphamide with four to eight doses of 1800 mg daratumumab. We followed clinical and immunological responses. Results The first patient with myeloperoxidase-ANCA-positive microscopic polyangiitis had resolution of pneumonitis and pleuritis and stabilisation of kidney function after daratumumab. The second patient with proteinase 3-ANCA-positive granulomatosis with polyangiitis, diffuse alveolar haemorrhage necessitating extracorporeal membrane oxygenation (ECMO) and acute kidney failure, requiring kidney replacement therapy, was weaned off ECMO, mechanical ventilation and dialysis and discharged home after daratumumab. Clinical improvement was paralleled by a strong reduction in serum ANCA levels as well as total IgG, indicating depletion of plasma cells. Apart from the depletion of CD38+ natural killer cells, blood leucocyte levels were not notably influenced by daratumumab. Only mild adverse events, such as hypogammaglobulinaemia and an upper respiratory tract infection occurred. Conclusion Daratumumab was safe and effective in inducing remission in two patients with severe treatment-refractory AAV, warranting prospective clinical trials to establish safety and efficacy.
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