Paris, France.
Leuven, Belgium.
Aliment Pharmacol Ther. 2021 May;53(10):1138-1146. doi: 10.1111/apt.16336. Epub 2021 Mar 25.
Obeticholic acid (OCA) and fibrates are second-line therapies for patients with primary biliary cholangitis (PBC) with an inadequate response to ursodeoxycholic acid (UDCA).
To know whether OCA and fibrates, administered together in combination with UDCA, have additive beneficial effects in patients with difficult-to-treat PBC.
PBC patients treated for ≥3 months with UDCA, OCA and fibrates (bezafibrate or fenofibrate) due to failure of either second-line therapy were included in a multicentre, uncontrolled retrospective cohort study. Changes in biochemical liver tests and pruritus were analysed using a generalised linear mixed-effect model.
Among 58 patients included, half received OCA as second-line and fibrates as third-line therapy (Group OCA-Fibrate), while the other half had the inverse therapeutic sequence (Group Fibrate-OCA). The mean duration of triple therapy was 11 months (range 3-26). Compared to dual therapy, triple therapy was associated with a significant gain in alkaline phosphatase (ALP) reduction: 22% per first year (95% CI 12%-31%), an effect that was stronger in OCA-Fibrate than in Fibrate-OCA group. Triple therapy was associated with a 3.4 (95% CI 1.4-8.2) odds ratio (OR) of reaching normal ALP and with a significant decrease in gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin. The ORs of achieving the Paris-2 and Toronto criteria of adequate biochemical response were 6.8 (95% CI 2.8-16.7) and 9.2 (95% CI 3.4-25.1) respectively. Finally, triple therapy significantly improved pruritus in OCA-Fibrate but not in Fibrate-OCA group.
Triple therapy with UDCA, OCA and fibrates is able to normalise biochemical liver tests and improve pruritus in patients with difficult-to-treat PBC.
对于对熊去氧胆酸（UDCA）治疗应答不足的原发性胆汁性胆管炎（PBC）患者，奥贝胆酸（OCA）和贝特类药物是二线治疗药物。
了解 OCA 和贝特类药物（非诺贝特或苯扎贝特）与 UDCA 联合应用，是否对治疗困难的 PBC 患者具有额外的有益作用。
对接受 UDCA、OCA 和贝特类药物（非诺贝特或苯扎贝特）治疗≥3 个月的 PBC 患者进行了一项多中心、非对照回顾性队列研究。采用广义线性混合效应模型分析生化肝功能检查和瘙痒的变化。
共纳入 58 例患者，其中 29 例患者先接受 OCA 二线治疗，后接受贝特类药物三线治疗（OCA-贝特组），29 例患者先接受贝特类药物二线治疗，后接受 OCA 三线治疗（贝特-OCA 组）。三联治疗的平均持续时间为 11 个月（范围 3-26 个月）。与双联治疗相比，三联治疗可显著降低碱性磷酸酶（ALP）：第一年降低 22%（95%CI 12%-31%），OCA-贝特组的效果强于贝特-OCA 组。三联治疗使 ALP 恢复正常的优势比（OR）为 3.4（95%CI 1.4-8.2），γ-谷氨酰转肽酶（GGT）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和总胆红素均显著降低。达到巴黎 2 期和多伦多标准的生化缓解的 OR 分别为 6.8（95%CI 2.8-16.7）和 9.2（95%CI 3.4-25.1）。最后，三联治疗可显著改善 OCA-贝特组的瘙痒，但对贝特-OCA 组无影响。
UDCA、OCA 和贝特类药物三联治疗可使治疗困难的 PBC 患者的生化肝功能检查恢复正常，并改善瘙痒。
