目的:我们进行了系统的文献综述,以了解支持与原发性胆汁性胆管炎(PBC)和原发性硬化性胆管炎(PSC)相关的胆汁淤积性瘙痒治疗决策的证据。
方法:纳入≥75%PBC或PSC参与者并报告与疗效相关的≥1个终点的研究,安全,纳入健康相关生活质量(HRQoL)或其他患者报告结局.使用Cochrane用于随机对照试验(RCT)的偏倚风险工具和用于非RCT的队列研究质量工具评估偏倚。
结果:确定了39种出版物,涵盖42项研究和6个治疗类别(包括研究和批准的产品):阴离子交换树脂,抗生素(利福平/衍生物),阿片类药物,选择性5-羟色胺再摄取抑制剂,贝多类,回肠胆汁酸转运蛋白抑制剂和其他不属于这六类的药物。在整个研究中,中位数样本量较小(n=18),20项研究超过20年,25例患者随访≤6周,只有25个是RCT。使用几种不同的工具评估瘙痒,它们的应用不一致。胆甾胺,考虑一线治疗中重度胆汁淤积性瘙痒,在六项研究(两项RCT)中进行了评估,其中包括56例PBC患者和2例PSC患者,只有三项研究证明了疗效,其中,两项RCT被评估为偏倚风险较高.其他药物类别的研究结果相似。
结论:缺乏关于疗效的一致和可重复的证据,对HRQoL的影响,胆汁淤积性瘙痒治疗的安全性,让医生依靠临床经验,而不是循证医学来选择治疗方法。
We conducted a systematic literature
review to understand the evidence supporting treatment decisions for cholestatic pruritus associated with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).
Studies that enrolled ≥ 75% participants with PBC or PSC and reported ≥ 1 endpoint(s) related to efficacy, safety, health-related quality of life (HRQoL) or other patient-reported outcomes were included. Bias was assessed using the Cochrane risk of bias tool for randomised controlled trials (RCTs) and the Quality of Cohort studies tool for non-RCTs.
Thirty-nine publications were identified, covering 42 studies and six treatment classes (including investigational and approved products): anion-exchange resins, antibiotics (rifampicin/derivatives), opiates, selective serotonin reuptake inhibitors, fibrates, ileal bile acid transporter inhibitors and other agents not categorised in these six classes. Across studies, median sample size was small (n = 18), 20 studies were over 20 years old, 25 followed patients for ≤ 6 weeks, only 25 were RCTs. Pruritus was assessed using several different tools, with inconsistencies in their application. Cholestyramine, considered first-line therapy for moderate-severe cholestatic pruritus, was assessed in six studies (two RCTs) including 56 patients with PBC and 2 with PSC, with evidence of efficacy demonstrated in only three studies, among which, two RCTs were assessed as having a high risk of bias. Findings were similar for other drug classes.
There is a lack of consistent and reproducible evidence available on efficacy, impact on HRQoL, and safety of cholestatic pruritus treatments, leaving physicians to rely on clinical experience rather than evidence-based medicine for treatment selection.