Supplementary Material for: Immunoadsorption Improves Remission Rates of Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Severe Kidney Involvement

<b><i>Introduction:</i></b> The role of plasma exchange in treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with severe kidney involvement is controversial. It is urgent to find effective treatments to improve prognosis of AAV patients. In this retrospective study, the outcomes of immunoadsorption (IA) onto protein A in AAV patients with severe kidney involvement were evaluated. <b><i>Methods:</i></b> Clinical data of 60 patients with AAV and severe kidney involvement were analyzed. Patients received cyclophosphamide or rituximab for remission induction, among which 16 were additionally treated with IA. Remission, end-stage kidney disease (ESKD), death, and relapse were compared. <b><i>Results:</i></b> Of 60 patients, 56 patients (93.3%) were positive for myeloperoxidase (MPO)-ANCA. At diagnosis, the estimated glomerular filtration rate and Birmingham Vasculitis Activity Score (BVAS) was 13.0 (7.7, 18.7) mL/min/1.73 m² and 11.1 ± 3.4, respectively. After 3–17 days (mean 10.4 days) of induction treatment, the disease activity decreased more obviously in the IA group (<i>p</i> = 0.022) than the control group. IA showed superior over standard regimen in clearance of MPO-ANCA within 3–31 days (median 11 days) after treatment (78.4% vs. 9.3%, <i>p</i> = 0.005). After a median follow-up of 20.2 months, remission was achieved more quickly (<i>p</i> = 0.035) and higher (hazard ratio (HR) = 2.3, 95% confidence interval (CI): 1.1∼7.2<i>, p</i> = 0.033) in the IA group than the control group. IA therapy showed an advantage in reducing death (HR = 0.2, 95% CI: 0.1∼0.9<i>, p</i> = 0.032). There was no difference in developing into ESKD in both groups (HR = 0.7, 95% CI: 0.3∼2.0<i>, p</i> = 0.504). Multivariate Cox regression analysis indicated that early-stage remission was an independent predictor for ESKD (HR = 0.03, 95% CI: 0.003∼0.25, <i>p</i> = 0.001) and death (HR = 0.07, 95% CI: 0.01∼0.51, <i>p</i> = 0.009). <b><i>Conclusion:</i></b> IA treatment induces quicker and higher remission and lower mortality in AAV patients with severe kidney involvement. The early remission independently predicts the outcomes for these patients.

<b><i>引言：</i></b> 血浆置换在伴重度肾脏受累的抗中性粒细胞胞浆抗体（antineutrophil cytoplasmic antibody, ANCA）相关性血管炎（antineutrophil cytoplasmic antibody-associated vasculitis, AAV）治疗中的作用尚存争议，目前亟需探索有效治疗手段以改善AAV患者的预后。本回顾性研究评估了蛋白A免疫吸附（immunoadsorption, IA）疗法对伴重度肾脏受累的AAV患者的临床疗效。<b><i>方法：</i></b> 本研究分析了60例伴重度肾脏受累的AAV患者的临床资料。所有患者均接受环磷酰胺或利妥昔单抗进行诱导缓解治疗，其中16例额外接受了IA治疗。对比两组患者的临床缓解情况、终末期肾病（end-stage kidney disease, ESKD）发生率、病死率及复发率。<b><i>结果：</i></b> 60例患者中，56例（93.3%）髓过氧化物酶（myeloperoxidase, MPO）-ANCA检测呈阳性。确诊时，患者的估算肾小球滤过率为13.0（7.7，18.7）mL/min/1.73 m²，伯明翰血管炎活动评分（Birmingham Vasculitis Activity Score, BVAS）为11.1±3.4。经过3~17天（平均10.4天）的诱导治疗后，IA组患者的疾病活动度下降程度较对照组更为显著（p=0.022）。在治疗后3~31天（中位时间11天）内，IA组在清除MPO-ANCA方面优于标准治疗方案（清除率分别为78.4% vs 9.3%，p=0.005）。中位随访20.2个月后，IA组患者的缓解速度更快（p=0.035），且总体缓解率更高（风险比（hazard ratio, HR）=2.3，95%置信区间（confidence interval, CI）：1.1~7.2，p=0.033）。IA治疗可显著降低患者病死率（HR=0.2，95%CI：0.1~0.9，p=0.032）。两组患者进展为ESKD的比例无显著差异（HR=0.7，95%CI：0.3~2.0，p=0.504）。多因素Cox回归分析显示，早期缓解是ESKD发生（HR=0.03，95%CI：0.003~0.25，p=0.001）及死亡（HR=0.07，95%CI：0.01~0.51，p=0.009）的独立预测因素。<b><i>结论：</i></b> IA治疗可使伴重度肾脏受累的AAV患者获得更快、更高比例的临床缓解，并降低病死率。早期缓解是此类患者预后的独立预测因子。