Abstract：
Thirty-to-forty percent of patients with primary biliary cholangitis inadequately respond to ursodeoxycholic acid. Our aim was to assemble national, real-world data on the effectiveness of obeticholic acid (OCA) as a second-line treatment, alongside non-licensed therapy with fibric acid derivatives (bezafibrate or fenofibrate).
This was a nationwide observational cohort study conducted from August 2017 until June 2021.
We accrued data from 457 patients; 349 treated with OCA and 108 with fibric acid derivatives. At baseline/pre-treatment, individuals in the OCA group manifest higher risk features compared with those taking fibric acid derivatives, evidenced by more elevated alkaline phosphatase values, and a larger proportion of individuals with cirrhosis, abnormal bilirubin, prior non-response to ursodeoxycholic acid, and elastography readings >9.6kPa (P < .05 for all). Overall, 259 patients (OCA) and 80 patients (fibric acid derivatives) completed 12 months of second-line therapy, yielding a dropout rate of 25.7% and 25.9%, respectively. At 12 months, the magnitude of alkaline phosphatase reduction was 29.5% and 56.7% in OCA and fibric acid groups (P < .001). Conversely, 55.9% and 36.4% of patients normalized serum alanine transaminase and bilirubin in the OCA group (P < .001). The proportion with normal alanine transaminase or bilirubin values in the fibric acid group was no different at 12 months compared with baseline. Twelve-month biochemical response rates were 70.6% with OCA and 80% under fibric acid treatment (P = .121). Response rates between treatment groups were no different on propensity-score matching or on sub-analysis of high-risk groups defined at baseline.
Across the population of patients with primary biliary cholangitis in the United Kingdom, rates of biochemical response and drug discontinuation appear similar under fibric acid and OCA treatment.
This was a nationwide observational cohort study conducted from August 2017 until June 2021.
We accrued data from 457 patients; 349 treated with OCA and 108 with fibric acid derivatives. At baseline/pre-treatment, individuals in the OCA group manifest higher risk features compared with those taking fibric acid derivatives, evidenced by more elevated alkaline phosphatase values, and a larger proportion of individuals with cirrhosis, abnormal bilirubin, prior non-response to ursodeoxycholic acid, and elastography readings >9.6kPa (P < .05 for all). Overall, 259 patients (OCA) and 80 patients (fibric acid derivatives) completed 12 months of second-line therapy, yielding a dropout rate of 25.7% and 25.9%, respectively. At 12 months, the magnitude of alkaline phosphatase reduction was 29.5% and 56.7% in OCA and fibric acid groups (P < .001). Conversely, 55.9% and 36.4% of patients normalized serum alanine transaminase and bilirubin in the OCA group (P < .001). The proportion with normal alanine transaminase or bilirubin values in the fibric acid group was no different at 12 months compared with baseline. Twelve-month biochemical response rates were 70.6% with OCA and 80% under fibric acid treatment (P = .121). Response rates between treatment groups were no different on propensity-score matching or on sub-analysis of high-risk groups defined at baseline.
Across the population of patients with primary biliary cholangitis in the United Kingdom, rates of biochemical response and drug discontinuation appear similar under fibric acid and OCA treatment.
摘要：
目的：30%-40%的原发性胆汁性胆管炎患者对熊去氧胆酸反应不充分。我们的目标是集结全国，关于奥贝胆酸(OCA)作为二线治疗有效性的真实世界数据，与非许可治疗与纤维酸衍生物（苯扎贝特或非诺贝特）。
方法：这是一项从2017年8月至2021年6月进行的全国性观察性队列研究。
结果：我们收集了457例患者的数据；349例患者接受OCA治疗，108例患者接受纤维酸衍生物治疗。在基线/治疗前，与服用纤维酸衍生物的人相比，OCA组中的个体表现出更高的风险特征，碱性磷酸酶值升高，和更大比例的肝硬化患者，胆红素异常,先前对熊去氧胆酸无反应，弹性成像读数>9.6kPa（P<0.05）。总的来说,259名患者（OCA）和80名患者（纤维酸衍生物）完成了12个月的二线治疗，辍学率分别为25.7%和25.9%,分别。12个月时,OCA和纤维酸组碱性磷酸酶降低幅度分别为29.5%和56.7%(P<.001)。相反，OCA组55.9%和36.4%的患者血清丙氨酸转氨酶和胆红素恢复正常(P<.001)。与基线相比，纤酸组丙氨酸转氨酶或胆红素值正常的比例在12个月时没有差异。使用OCA的12个月生化反应率为70.6％，在纤维酸处理下为80％（P=0.121）。治疗组之间的反应率在倾向评分匹配或基线定义的高风险组的亚分析上没有差异。
结论：在英国原发性胆汁性胆管炎患者中，在纤维酸和OCA治疗下，生化反应和药物停药率相似。
方法：这是一项从2017年8月至2021年6月进行的全国性观察性队列研究。
结果：我们收集了457例患者的数据；349例患者接受OCA治疗，108例患者接受纤维酸衍生物治疗。在基线/治疗前，与服用纤维酸衍生物的人相比，OCA组中的个体表现出更高的风险特征，碱性磷酸酶值升高，和更大比例的肝硬化患者，胆红素异常,先前对熊去氧胆酸无反应，弹性成像读数>9.6kPa（P<0.05）。总的来说,259名患者（OCA）和80名患者（纤维酸衍生物）完成了12个月的二线治疗，辍学率分别为25.7%和25.9%,分别。12个月时,OCA和纤维酸组碱性磷酸酶降低幅度分别为29.5%和56.7%(P<.001)。相反，OCA组55.9%和36.4%的患者血清丙氨酸转氨酶和胆红素恢复正常(P<.001)。与基线相比，纤酸组丙氨酸转氨酶或胆红素值正常的比例在12个月时没有差异。使用OCA的12个月生化反应率为70.6％，在纤维酸处理下为80％（P=0.121）。治疗组之间的反应率在倾向评分匹配或基线定义的高风险组的亚分析上没有差异。
结论：在英国原发性胆汁性胆管炎患者中，在纤维酸和OCA治疗下，生化反应和药物停药率相似。
