UK-Wide Multicenter Evaluation of Second-line Therapies in Primary Biliary Cholangitis

Nadir Abbas, Emma L. Culver, Douglas Thorburn, Neil Halliday, Hannah Crothers, Jessica K. Dyson, April Phaw, Richard Aspinall, Salim I. Khakoo, Yiannis Kallis, Belinda Smith, Imran Patanwala, Anne McCune, Chenchu R. Chimakurthi, Vinod Hegade, Michael Orrell, Rebecca Jones, George Mells, Colette Thain, Robert-Mitchell ThainDavid Jones, Gideon Hirschfield, Palak J. Trivedi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)1561-1570.e13
Number of pages23
JournalClinical Gastroenterology and Hepatology
Volume21
Issue number6
Early online date9 Aug 2022
DOIs
Publication statusPublished - Jun 2023

Keywords

  • Bezafibrate
  • Cirrhosis
  • Fenofibrate
  • Fibric Acid
  • Obeticholic Acid
  • Cholestasis
  • Farnesoid-X-receptor (FXR)
  • Fibrates
  • Peroxisome Proliferator Activated Receptor (PPAR)

Fingerprint

Dive into the research topics of 'UK-Wide Multicenter Evaluation of Second-line Therapies in Primary Biliary Cholangitis'. Together they form a unique fingerprint.

Cite this