School of Pharmacy, University College London, London, UK.
Berkshire Kidney Unit, Royal Berkshire Hospital, Reading, UK.
Scand J Rheumatol. 2023 Sep;52(5):564-573. doi: 10.1080/03009742.2023.2211387. Epub 2023 Jun 20.
Glucocorticoids (GCs) remain a cornerstone of the initial management of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), but have several dose-dependent side effects, in particular infections. The optimal dosing and tapering of oral GCs for remission induction are unknown. A systematic review and meta-analysis was undertaken to determine the efficacy and safety of low- versus high-dose GC regimens.
A systematic search of MEDLINE, Embase, and PubMed databases was conducted. Clinical studies using a GC-based induction protocol were selected. A daily dose of 0.5 mg/kg or < 30 mg/day oral prednisolone equivalent by the start of week 4 of the induction tapering schedule marked the threshold between high- and low-dose GCs. Risk ratios (RRs) were calculated by the random effects model for outcomes of remission and infection. Relapse events were summarized using risk differences with 95% confidence intervals (CIs).
In total, 1145 participants were included in three randomized controlled trials and two observational studies, of whom 543 were assigned to the low-dose GC group and 602 to the high-dose GC group. A low-dose GC regimen was non-inferior to high-dose GCs with respect to outcomes of remission (RR 0.98, 95% CI 0.95-1.02, p = 0.37; I = 0%) and relapse (risk difference 0.03, 95% CI -0.01 to 0.06, p = 0.15; I = 12%), while significantly reducing the incidence of infection (RR 0.60, 95% CI 0.39-0.91, p = 0.02; I = 65%).
Studies with low-dose GC regimens in AAV are associated with fewer infections while obtaining equivalent efficacy.
糖皮质激素(GCs)仍然是抗中性粒细胞胞质抗体(ANCA)相关性血管炎(AAV)初始治疗的基石,但具有许多剂量依赖性副作用,特别是感染。对于缓解诱导,口服 GCs 的最佳剂量和逐渐减量尚不清楚。本系统评价和荟萃分析旨在确定低剂量与高剂量 GC 方案的疗效和安全性。
对 MEDLINE、Embase 和 PubMed 数据库进行系统检索。选择使用基于 GC 的诱导方案的临床研究。在诱导减量方案的第 4 周开始时,每天 0.5mg/kg 或 <30mg/天的口服泼尼松龙等效剂量标志着高剂量和低剂量 GCs 的阈值。使用随机效应模型计算缓解和感染结局的风险比(RR)。使用风险差异和 95%置信区间(CI)总结复发事件。
共有 1145 名参与者纳入三项随机对照试验和两项观察性研究,其中 543 名参与者被分配到低剂量 GC 组,602 名参与者被分配到高剂量 GC 组。低剂量 GC 方案在缓解结局方面不劣于高剂量 GCs(RR 0.98,95%CI 0.95-1.02,p = 0.37;I = 0%)和复发(风险差异 0.03,95%CI -0.01 至 0.06,p = 0.15;I = 12%),同时显著降低感染发生率(RR 0.60,95%CI 0.39-0.91,p = 0.02;I = 65%)。
AAV 中低剂量 GC 方案的研究与较低的感染率相关,同时获得等效疗效。