Author information

¹Department of Population Health Sciences, Duke University, Durham, NC, USA.

²Target RWE, Durham, NC, USA.

³Intercept Pharmaceuticals, Morristown, NJ, USA.

⁴Real World Evidence, Syneos Health, NC, USA.

⁵Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam, Netherlands.

⁶IHPME University of Toronto, Toronto, Ontario, Canada.

⁷Toronto Centre for Liver Disease and TGHRI, University Health Network, Toronto, Ontario, Canada.

⁸Liver Institute Northwest and Elson S. Floyd College of Medicine, Washington State University, Seattle, WA, USA.

⁹Newcastle University, Newcastle upon Tyne, UK.

¹⁰Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.

¹¹Academic Department of Medical Genetics, University of Cambridge, Cambridge, UK.

¹²National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre, Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.

¹³Optum Epidemiology, Boston, MA, USA.

Abstract

Background and aims: Primary biliary cholangitis (PBC) is a rare, progressive liver disease. Obeticholic acid (OCA) received accelerated approval for treating patients with PBC in whom ursodeoxycholic acid (UDCA) failed, based on a surrogate endpoint of reduction in alkaline phosphatase. Analysis of the long-term safety extension with 2 external control groups demonstrated a significant increase in event-free survival in OCA-treated patients. This fully real-world evidence study assessed the effect of OCA treatment on the clinical outcomes.

Approach and results: This trial emulation used data from the Komodo Healthcare Map™ claims database linked to US national laboratory, transplant, and death databases. Patients with compensated PBC and intolerance/inadequate response to UDCA who initiated OCA therapy were compared with patients who were OCA-eligible but not OCA-treated. The primary endpoint was time to first occurrence of death, liver transplant, or hospitalization for hepatic decompensation, analyzed using a propensity-score weighted Cox proportional hazards model. Baseline prognostic factors were balanced using standardized morbidity ratio weighting. For the primary analysis, 4174 patients contributed 11,246 control index dates; 403 patients contributed OCA indexes. Weighted groups were well balanced. Median (95% CI) follow-up in the OCA and non-OCA arms was 9.3 (8.4-10.6) months and 17.5 (16.2-18.6) months (weighted population; censored at discontinuation). Eight events occurred in the OCA arm, 32 in the weighted control (HR=0.37; 95% CI=0.14-0.75; p<0.001). Effects were consistent for each component of the composite endpoint.

Conclusions: We identified a 63% reduced risk of hospitalization for hepatic decompensation, liver transplant, or death in OCA-treated versus non-OCA-treated individuals.

Trial registration: HEROES; ClinicalTrials.gov NCT05292872.