Department of Rheumatology, IRCCS Policlinico S. Matteo Foundation, University of Pavia, Pavia, Italy; University of Pavia, PhD in Experimental Medicine, Pavia, Italy.
Division of Rheumatology, MedStar Georgetown University Hospital, Washington, DC, USA; Systemic Autoimmunity Branch, National Institutes of Health, NIAMS, Bethesda, MD, USA.
Semin Arthritis Rheum. 2020 Dec;50(6):1314-1325. doi: 10.1016/j.semarthrit.2020.09.010. Epub 2020 Sep 29.
A comprehensive review of outcome measures used in randomized controlled trials (RCTs) of ANCA-associated vasculitis (AAV) could advance trial conductance for this disease.
A systematic literature review of outcome measures (as specified in methods section as primary and/or secondary outcomes) in RCTs of AAV was conducted. Medline, Cochrane CENTRAL, and ClinicalTrials.gov were searched from inception until April 30, 2019 for RCTs enrolling patients with granulomatosis with polyangiitis and/or microscopic polyangiitis. Outcome measures were organized according to domains (e.g. disease activity) and instruments [e.g. Birmingham Vasculitis Activity Score (BVAS)].
Out of 1101 identified records, 68 RCTs were eligible. Disease activity was an outcome domain collected in 67 (98%) of the RCTs. The BVAS was the most widely used instrument for disease assessment but definitions for remissions and relapse varied for the purpose of primary endpoint definitions. Damage, most often assessed by the Vasculitis Damage Index, was an outcome in 30 (44%) of the RCTs. Mortality was specified as an outcome in 26 (38%) studies. The following outcome domains were assessed: patient-reported outcomes (PROs) in 28 (41%), drug exposure/safety in 58 (85%), and biomarkers [acute phase reactants, ANCA levels] in 24 (35%). Timing for outcome assessment differed substantially, with 3, 6, or 12 months being the most frequent time points.
Outcome measures used in trials in AAV commonly included vasculitis-specific tools for disease assessment, but with heterogeneity in endpoint-definitions and timing of assessments. Other core outcomes in AAV, including PROs, and damage measures, are often omitted in AAV trials.
对 ANCA 相关性血管炎 (AAV) 的随机对照试验 (RCT) 中使用的结局测量进行全面综述，可推进该疾病的试验进行。
对 AAV 的 RCT 中（如方法部分中规定的主要和/或次要结局）使用的结局测量进行系统文献回顾。从建库到 2019 年 4 月 30 日，在 Medline、Cochrane 中心数据库和 ClinicalTrials.gov 中检索了纳入肉芽肿性多血管炎和/或显微镜下多血管炎患者的 RCT。根据领域（如疾病活动度）和工具（如伯明翰血管炎活动评分 (BVAS)）对结局测量进行组织。
在 1101 条鉴定记录中，有 68 项 RCT 符合纳入标准。67 项（98%）RCT 中均收集了疾病活动度这一结局领域。BVAS 是最广泛用于疾病评估的工具，但缓解和复发的定义因主要结局定义而异。30 项（44%）RCT 中评估了损伤，最常使用的是血管炎损伤指数。26 项（38%）研究中明确了死亡率作为结局。评估了以下结局领域：28 项（41%）研究中患者报告结局（PROs），58 项（85%）研究中药物暴露/安全性，24 项（35%）研究中生物标志物[急性期反应物、ANCA 水平]。结局评估的时间差异很大，最常见的时间点是 3、6 或 12 个月。
AAV 试验中使用的结局测量通常包括用于疾病评估的血管炎特异性工具，但终点定义和评估时间存在异质性。AAV 试验中经常忽略其他核心结局，包括 PROs 和损伤指标。
