UK-wide multicenter evaluation of second-line therapies in primary biliary cholangitis
Abbas, Nadir Culver, Emma L Thorburn, Douglas Halliday, Neil Crothers, Hannah Dyson, Jessica K Phaw, April Aspinall, Richard Khakoo, Salim I Kallis, Yiannis
Abbas, Nadir
Culver, Emma L
Thorburn, Douglas
Halliday, Neil
Crothers, Hannah
Dyson, Jessica K
Phaw, April
Aspinall, Richard
Khakoo, Salim I
Kallis, Yiannis
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2022-08-09
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Abstract
Background & aims: 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).
Methods: This was a nationwide observational cohort study conducted from August 2017 until June 2021.
Results: 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.
Conclusion: 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.
Keywords: Bezafibrate; Cholestasis; Cirrhosis; Farnesoid-X-receptor (FXR); Fenofibrate; Fibrates; Fibric Acid; Obeticholic Acid; Peroxisome Proliferator Activated Receptor (PPAR).
Citation
Clin Gastroenterol Hepatol . 2023 Jun;21(6):1561-1570.e13
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Article