From the Population Health Research Institute, McMaster University-Hamilton Health Sciences (M.W.), and the Departments of Medicine (M.W., N.K.) and Health Research Methods, Evidence, and Impact (M.W.), McMaster University, and St. Joseph's Healthcare (M.W., N.K., A.M.), Hamilton, ON, the Division of Nephrology and the Li Ka Shing Knowledge Institute, St. Michael's Hospital (R.W.), and the Department of Medicine (R.W.), the Vasculitis Clinic, Department of Rheumatology (C.P., S.C.), and Mount Sinai Hospital, Division of Rheumatology (C.P., S.C.), University of Toronto, Toronto, the Department of Medicine, University of Calgary, Calgary, AB (L.P.G.), the Department of Medicine, University of British Columbia, Vancouver (A.L.), and the Department of Medicine, University of Western Ontario, London (W.F.C.) - all in Canada; the Division of Rheumatology, Departments of Medicine and Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia (P.A.M., C.A.M.); Royal Adelaide Hospital and the University of Adelaide, Adelaide (C.-A.P.), and the Australasian Kidney Trials Network, University of Queensland, Brisbane (C.M.H., D.R.) - all in Australia; Rigshospitalet University Hospital, Department of Nephrology, Copenhagen (W.M.S.); Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Université Paris Descartes, Paris (X.P., L.G.); the Faculty of Medicine, University of Miyazaki, Miyazaki (S.F.), and the Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, and the Clinical and Translational Research Center, University Hospital, Kyoto Prefectural University of Medicine, Kyoto (T.I.-I.) - all in Japan; Royal Berkshire Hospital, Reading (O.F.), the Institute of Clinical Sciences (L.H.) and the Birmingham Clinical Trials Unit, Institute of Applied Health Research (S.M., N.I.), University of Birmingham, Birmingham, the Royal Devon and Exeter NHS Foundation Trust, Exeter (L.S.), the Department of Medicine, Imperial College London (C.D.P.), and Guys and St. Thomas' NHS Foundation Trust (A.L.C.), London, and the Department of Medicine, University of Cambridge (B.B., E.B., D.R.W.J.), and Addenbrooke's Hospital (D.R.W.J.), Cambridge - all in the United Kingdom; Spedali Civili di Brescia, Università di Brescia, Brescia, Italy (G.G.); the Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN (U.S.); the Department of Nephrology, General University Hospital, Charles University, Prague, Czech Republic (V.T.); the Renal Service, Waitemata District Health Board, and the Department of Medicine, University of Auckland, Auckland, New Zealand (J.R.Z.); Jagiellonian University Medical College, Krakow, Poland (W.S.); and the Primary Systemic Vasculitides Clinic, Instituto Nacional de Enfermedades Respiratorias, Mexico City (L.F.F.-S.).
N Engl J Med. 2020 Feb 13;382(7):622-631. doi: 10.1056/NEJMoa1803537.
More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis.
We conducted a randomized trial with a 2-by-2 factorial design to evaluate the use of plasma exchange and two regimens of oral glucocorticoids in patients with severe ANCA-associated vasculitis (defined by an estimated glomerular filtration rate of <50 ml per minute per 1.73 m of body-surface area or diffuse pulmonary hemorrhage). Patients were randomly assigned to undergo plasma exchange (seven plasma exchanges within 14 days after randomization) or no plasma exchange (control group). Patients were also randomly assigned to follow either a standard-dose regimen or a reduced-dose regimen of oral glucocorticoids. Patients were followed for up to 7 years for the primary composite outcome of death from any cause or end-stage kidney disease (ESKD).
Death from any cause or ESKD occurred in 100 of 352 patients (28.4%) in the plasma-exchange group and in 109 of 352 patients (31.0%) in the control group (hazard ratio, 0.86; 95% confidence interval [CI], 0.65 to 1.13; P = 0.27). The results were similar in subgroup analyses and in analyses of secondary outcomes. We also assessed the noninferiority of a reduced-dose regimen of glucocorticoids to a standard-dose regimen, using a noninferiority margin of 11 percentage points. Death from any cause or ESKD occurred in 92 of 330 patients (27.9%) in the reduced-dose group and in 83 of 325 patients (25.5%) in the standard-dose group (absolute risk difference, 2.3 percentage points; 90% CI, -3.4 to 8.0), which met the criterion for noninferiority. Serious infections at 1 year were less common in the reduced-dose group than in the standard-dose group (incidence rate ratio, 0.69; 95% CI, 0.52 to 0.93), but other secondary outcomes were similar in the two groups.
Among patients with severe ANCA-associated vasculitis, the use of plasma exchange did not reduce the incidence of death or ESKD. A reduced-dose regimen of glucocorticoids was noninferior to a standard-dose regimen with respect to death or ESKD. (Funded by the U.K. National Institute for Health Research and others; PEXIVAS Current Controlled Trials number, ISRCTN07757494; ClinicalTrials.gov number, NCT00987389.).
需要更有效和更安全的治疗方法来治疗抗中性粒细胞胞浆抗体（ANCA）相关性血管炎。
我们进行了一项随机试验，采用 2×2 析因设计来评估血浆置换和两种口服糖皮质激素方案在严重 ANCA 相关性血管炎（定义为估计肾小球滤过率<50ml/min/1.73m2 或弥漫性肺出血）患者中的应用。患者被随机分配接受血浆置换（随机分组后 14 天内进行 7 次血浆置换）或不接受血浆置换（对照组）。患者还被随机分配接受标准剂量方案或低剂量方案的口服糖皮质激素治疗。患者接受了长达 7 年的随访，以评估主要复合终点（任何原因导致的死亡或终末期肾病（ESKD））。
在血浆置换组的 352 例患者中有 100 例（28.4%）和对照组的 352 例患者中有 109 例（31.0%）发生了任何原因导致的死亡或 ESKD（风险比，0.86；95%置信区间[CI]，0.65 至 1.13；P=0.27）。亚组分析和次要结局分析结果相似。我们还使用 11 个百分点的非劣效性边界评估了糖皮质激素低剂量方案与标准剂量方案的非劣效性。在低剂量组的 330 例患者中有 92 例（27.9%）和标准剂量组的 325 例患者中有 83 例（25.5%）发生了任何原因导致的死亡或 ESKD（绝对风险差异，2.3%；90%CI，-3.4 至 8.0），符合非劣效性标准。低剂量组在 1 年内发生严重感染的情况少于标准剂量组（发生率比，0.69；95%CI，0.52 至 0.93），但两组的其他次要结局相似。
在严重 ANCA 相关性血管炎患者中，使用血浆置换并未降低死亡或 ESKD 的发生率。糖皮质激素低剂量方案与标准剂量方案相比，在死亡或 ESKD 方面不劣效。（由英国国家卫生研究院和其他机构资助；PEXIVAS 当前对照试验编号，ISRCTN07757494；ClinicalTrials.gov 编号，NCT00987389。）
