Xu Chenyi, Yue Rensong, Lv Xuelian, Wang Shengnan, Du Mengmeng
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Xinjin Hospital of Traditional Chinese Medicine, Chengdu, China.
Front Pharmacol. 2022 Oct 20;13:835991. doi: 10.3389/fphar.2022.835991. eCollection 2022.
Pruritus is a common complication in patients with primary biliary cholangitis (PBC). The pathogenesis is not clear, and also the precise therapeutic measures remain alluring. In order to systematically evaluate the efficacy and safety of drug interventions in the treatment of pruritus associated with PBC, this systemic review and meta-analysis was conducted. The randomized controlled trials (RCTs) on drug interventions in the treatment of pruritus associated with primary cholangitis were searched in the electronic databases of PubMed, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov. Two researchers independently screened the literature, extracted and integrated the data, and assessed the bias risk of the selected literature, according to the . Finally, the STATA 15.0 software was used for the meta-analysis. A total of 23 RCTs involving 2,194 patients were studied, that included 12 pharmacological interventions. In terms of itching relief, compared with placebo, UDCA, methotrexate and GSK2330672 had a definite effect in improving pruritus (pruritus remission rate before and after treatment, 0.05). In terms of serum indexes, compared with placebo group, UDCA, OCA, rifampicin, cyclosporine, NGM282, seladelpar and colchicine may improve blood alkaline phosphatase (ALP) ( 0.05), but only rifampicin showed low heterogeneity. UDCA, bezafibrate, OCA, rifampicin, NGM282 and others may improve blood γ-glutamyl transpeptidase (γ-GGT) ( 0.05), but due to the high heterogeneity and the limitation of research samples, a clear conclusion cannot be drawn. In terms of adverse events, except high (>15 mg/kg/day) and low doses (<13 mg/kg/day) of UDCA increased the incidence of adverse events, there were no risk of increasing the incidence of adverse events compared with placebo ( 0.05), and a moderate dose of UDCA (13-15 mg/kg/day) and malotilate (1,500 mg/day) may also help in reducing the incidence of adverse events ( 0.05). UDCA, methotrexate and GSK2330672 may relieve itching in patients with PBC, but there is a lack of robust evidence to support their effect on ALP or γ-GGT. Due to the heterogeneity in the published studies, based on the present review, we cannot explicitly recommend any specific drug for the treatment of PBC-related pruritus. link-https://osf.io/2g8ya, identifier 10.17605/OSF.IO/2G8YA.
瘙痒是原发性胆汁性胆管炎（PBC）患者的常见并发症。其发病机制尚不清楚，确切的治疗措施也仍具吸引力。为了系统评价药物干预治疗PBC相关瘙痒的疗效和安全性，进行了这项系统评价和荟萃分析。在PubMed、EMBASE、Cochrane图书馆、科学网和ClinicalTrials.gov的电子数据库中检索了关于药物干预治疗原发性胆管炎相关瘙痒的随机对照试验（RCT）。两名研究人员根据相关标准独立筛选文献、提取和整合数据，并评估所选文献的偏倚风险。最后，使用STATA 15.0软件进行荟萃分析。共纳入23项RCT，涉及2194例患者，包括12种药物干预措施。在瘙痒缓解方面，与安慰剂相比，熊去氧胆酸（UDCA）、甲氨蝶呤和GSK2330672在改善瘙痒方面有确切效果（治疗前后瘙痒缓解率，P<0.05）。在血清指标方面，与安慰剂组相比，UDCA、奥贝胆酸（OCA）、利福平、环孢素、NGM282、司美格鲁肽和秋水仙碱可能改善血碱性磷酸酶（ALP）（P<0.05），但只有利福平显示低异质性。UDCA、苯扎贝特、OCA、利福平、NGM282等可能改善血γ-谷氨酰转肽酶（γ-GGT）（P<0.05），但由于异质性高和研究样本的局限性，无法得出明确结论。在不良事件方面，除高剂量（>15mg/kg/天）和低剂量（<13mg/kg/天）的UDCA增加不良事件发生率外，与安慰剂相比无增加不良事件发生率的风险（P<0.05），中等剂量的UDCA（13 - 15mg/kg/天）和马洛替酯（1500mg/天）也可能有助于降低不良事件发生率（P<0.05）。UDCA、甲氨蝶呤和GSK2330672可能缓解PBC患者的瘙痒，但缺乏有力证据支持它们对ALP或γ-GGT的作用。由于已发表研究存在异质性，基于本综述，我们无法明确推荐任何特定药物用于治疗PBC相关瘙痒。链接 - https://osf.io/2g8ya，标识符10.17605/OSF.IO/2G8YA。
