UK-Wide Multicentre Evaluation of Second Line Therapies in Primary Biliary Cholangitis.

BACKGROUND AND AIMS: One-third of patients with primary biliary cholangitis (PBC) inadequately respond to ursodeoxycholic acid (UDCA). 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/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 to those taking fibric acid derivatives, evidenced by more elevated ALP values, and a larger proportion of individuals with cirrhosis, abnormal bilirubin, prior non-response to UDCA, and elastography readings >9.6kPa (P<0.05 for all). Overall, 259 (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 ALP reduction was 29.5% and 56.7% in OCA and fibric acid groups (P<0.001). Conversely, 55.9% and 36.4% of patients normalised serum alanine transaminase (ALT) and bilirubin in the OCA group (P<0.001). The proportion with normal ALT or bilirubin values in the fibric acid group was no different at 12 months compared to baseline. Twelve-month biochemical response rates were 70.6% with OCA and 80% under fibric acid treatment (P=0.121). 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 UK-PBC population, rates of biochemical response and drug discontinuation appear similar under fibric acid and OCA treatment.