Pharmacy department/Evidence-based pharmacy centre, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.
BMJ. 2022 Feb 25;376:e064597. doi: 10.1136/bmj-2021-064597.
What is the role of plasma exchange and what is the optimal dose of glucocorticoids in the first 6 months of therapy of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)? This guideline was triggered by the publication of a new randomised controlled trial.
Existing guideline recommendations vary regarding the use of plasma exchange in AAV and lack explicit recommendations regarding the tapering regimen of glucocorticoids during induction therapy.
The guideline panel makes a weak recommendation against plasma exchange in patients with low or low-moderate risk of developing end stage kidney disease (ESKD), and a weak recommendation in favour of plasma exchange in patients with moderate-high or high risk of developing ESKD. For patients with pulmonary haemorrhage without renal involvement, the panel suggests not using plasma exchange (weak recommendation). The panel made a strong recommendation in favour of a reduced dose rather than standard dose regimen of glucocorticoids, which involves a more rapid taper rate and lower cumulative dose during the first six months of therapy.
A guideline panel including patients, a care giver, clinicians, content experts, and methodologists produced these recommendations using GRADE and in adherence with standards for trustworthy guidelines. The recommendations are based on two linked systematic reviews. The panel took an individual patient perspective in the development of recommendations.
The systematic review of plasma exchange identified nine randomised controlled trials (RCTs) that enrolled 1060 patients with AAV. Plasma exchange probably has little or no effect on mortality or disease relapse (moderate and low certainty). Plasma exchange probably reduces the one year risk of ESKD (approximately 0.1% reduction in those with low risk, 2.1% reduction in those with low-moderate risk, 4.6% reduction in those with moderate-high risk, and 16.0% reduction in those with high risk or requiring dialysis) but increases the risk of serious infections (approximately 2.7% increase in those with low risk, 4.9% increase in those with low-moderate risk, 8.5% increase in those with moderate-high risk, to 13.5% in high risk group) at 1 year (moderate to high certainty). The guideline panel agreed that most patients with low or low-moderate risk of developing ESKD would consider the harms to outweigh the benefits, while most of those with moderate-high or high risk would consider the benefits to outweigh the harms. For patients with pulmonary haemorrhage without kidney involvement, based on indirect evidence, plasma exchange may have little or no effect on death (very low certainty) but may have an important increase in serious infections at 1 year (approximately 6.8% increase, low certainty). The systematic review of different dose regimens of glucocorticoids identified two RCTs at low risk of bias with 704 and 140 patients respectively. A reduced dose regimen of glucocorticoid probably reduces the risk of serious infections by approximately 5.9% to 12.8% and probably does not increase the risk of ESKD at the follow-up of 6 months to longer than 1 year (moderate certainty for both outcomes).
The recommendations were made with the understanding that patients would place a high value on reduction in ESKD and less value on avoiding serious infections. The panel concluded that most (50-90%) of fully informed patients with AAV and with low or low-moderate risk of developing ESKD with or without pulmonary haemorrhage would decline plasma exchange, whereas most patients with moderate-high or high risk or requiring dialysis with or without pulmonary haemorrhage would choose to receive plasma exchange. The panel also inferred that the majority of fully informed patients with pulmonary haemorrhage without kidney involvement would decline plasma exchange and that all or almost all (≥90%) fully informed patients with AAV would choose a reduced dose regimen of glucocorticoids during the first 6 months of therapy.
在抗中性粒细胞胞质抗体（ANCA）相关性血管炎（AAV）患者治疗的前 6 个月中，血浆置换的作用是什么，糖皮质激素的最佳剂量是多少？本指南是由一项新的随机对照试验引发的。
现有的指南建议在 AAV 中使用血浆置换的方法存在差异，并且在诱导治疗期间糖皮质激素的减量方案方面缺乏明确的建议。
指南小组对低危或中低危发生终末期肾病（ESKD）风险的患者强烈反对使用血浆置换，对中高危或高危发生 ESKD 风险的患者则强烈建议使用血浆置换。对于没有肾脏受累的肺出血患者，小组建议不使用血浆置换（弱推荐）。小组建议采用减少剂量而不是标准剂量方案的糖皮质激素，这涉及在前 6 个月治疗期间更快的减量速度和更低的累积剂量。
一个包括患者、照顾者、临床医生、内容专家和方法学家在内的指南小组使用 GRADE 并遵循可信指南的标准制定了这些建议。这些建议是基于两项相关的系统评价。小组在制定建议时从患者个体的角度出发。
血浆置换的系统评价确定了 9 项随机对照试验（RCTs），共纳入了 1060 例 AAV 患者。血浆置换可能对死亡率或疾病复发几乎没有影响或影响较小（中等和低确定性）。血浆置换可能降低 ESKD 的一年风险（在低危患者中减少约 0.1%，在低中危患者中减少 2.1%，在中高危患者中减少 4.6%，在高危或需要透析的患者中减少 16.0%），但增加严重感染的风险（在低危患者中增加约 2.7%，在低中危患者中增加 4.9%，在中高危患者中增加 8.5%，在高危组中增加 13.5%）在 1 年时（中等至高确定性）。指南小组一致认为，大多数低危或低中危发生 ESKD 风险的患者将认为危害大于益处，而大多数中高危或高危患者将认为益处大于危害。对于没有肾脏受累的肺出血患者，基于间接证据，血浆置换可能对死亡几乎没有影响（极低确定性），但可能会导致 1 年内严重感染的重要增加（约 6.8%的增加，低确定性）。不同剂量糖皮质激素方案的系统评价确定了两项低偏倚风险的 RCT，分别有 704 名和 140 名患者。糖皮质激素的减少剂量方案可能会降低严重感染的风险，约为 5.9%至 12.8%，并且在 6 个月至 1 年以上的随访中可能不会增加 ESKD 的风险（对两种结局均为中等确定性）。
建议是在患者高度重视降低 ESKD 和不太重视避免严重感染的前提下提出的。小组得出结论，大多数（50-90%）完全知情的 AAV 患者，无论是否伴有肺出血，低危或低中危发生 ESKD 的风险，都将拒绝接受血浆置换，而大多数中高危或高危或需要透析的患者，无论是否伴有肺出血，都会选择接受血浆置换。小组还推断，大多数完全知情的肺出血患者没有肾脏受累，将拒绝接受血浆置换，大多数完全知情的 AAV 患者（≥90%）在前 6 个月的治疗中会选择糖皮质激素的减少剂量方案。
