Gulati Kavita, Edwards Helena, Prendecki Maria, Cairns Thomas D, Condon Marie, Galliford Jack, Griffith Megan, Levy Jeremy B, Tam Frederick W K, Tanna Anisha, Pusey Charles D, McAdoo Stephen P
Vasculitis Clinic, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK; Centre for Inflammatory Disease, Immunology & Inflammation, Imperial College London, London, UK.
Vasculitis Clinic, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK.
Kidney Int. 2021 Dec;100(6):1316-1324. doi: 10.1016/j.kint.2021.08.025. Epub 2021 Sep 22.
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis can present with life-threatening lung-kidney syndromes. However, many controlled treatment trials excluded patients with diffuse alveolar hemorrhage or severely impaired glomerular filtration rates, and so the optimum treatment in these cases is unclear. In this retrospective cohort study, we report the outcomes of 64 patients with life-threatening disease treated with a combination regimen of rituximab, low-dose intravenous cyclophosphamide, oral glucocorticoids, and plasma exchange. At entry, the median estimated glomerular filtration rate was 9 mL/min, 47% of patients required dialysis, and 52% had diffuse alveolar hemorrhage. All patients received a minimum of seven plasma exchanges, and the median cumulative doses of rituximab, cyclophosphamide, and glucocorticoid were 2, 3, and 2.6 g, respectively, at six months. A total of 94% of patients had achieved disease remission (version 3 Birmingham Vasculitis Activity Score of 0) at this time point, and 67% of patients who required dialysis recovered independent kidney function. During long-term follow-up (median duration 46 months), overall patient survival was 85%, and 69% of patients remained free from end-stage kidney disease, which compares favorably to a historic cohort with severe disease treated with a conventional induction regimen. Combination treatment was associated with prolonged B cell depletion and low rates of relapse; 87% of patients were in continuous remission at month 36. The serious infection rate during total follow-up was 0.28 infections/patient/year, suggesting that combination treatment is not associated with an enduring risk of infection. Thus, we suggest that combination immunosuppressive therapy may permit glucocorticoid avoidance and provide rapid and prolonged disease control in patients with severe ANCA-associated vasculitis.
抗中性粒细胞胞浆抗体（ANCA）相关血管炎可表现为危及生命的肺-肾综合征。然而，许多对照治疗试验排除了弥漫性肺泡出血或肾小球滤过率严重受损的患者，因此这些病例的最佳治疗方法尚不清楚。在这项回顾性队列研究中，我们报告了64例患有危及生命疾病的患者接受利妥昔单抗、低剂量静脉注射环磷酰胺、口服糖皮质激素和血浆置换联合方案治疗的结果。入院时，估计肾小球滤过率中位数为9 mL/分钟，47%的患者需要透析，52%的患者有弥漫性肺泡出血。所有患者至少接受了7次血浆置换，6个月时利妥昔单抗、环磷酰胺和糖皮质激素的累积剂量中位数分别为2 g、3 g和2.6 g。此时共有94%的患者实现了疾病缓解（伯明翰血管炎活动评分3版为0），67%需要透析的患者恢复了独立肾功能。在长期随访（中位持续时间46个月）中，患者总体生存率为85%，69%的患者未发生终末期肾病，这与采用传统诱导方案治疗的严重疾病历史队列相比具有优势。联合治疗与B细胞耗竭时间延长和复发率低相关；87%的患者在第36个月时持续缓解。总随访期间严重感染率为0.28次感染/患者/年，表明联合治疗与持续感染风险无关。因此，我们建议联合免疫抑制治疗可能允许避免使用糖皮质激素，并为重症ANCA相关血管炎患者提供快速且持久的疾病控制。
