Patients who received obeticholic acid for primary biliary cholangitis experienced greater transplant-free survival compared with external control patients, according to research published in Gastroenterology.

“This important study is the first to demonstrate that initiating treatment with obeticholic acid (OCA) in appropriate patients with primary biliary cholangitis (PBC) appears to have a meaningful impact on clinical outcomes,” Gideon Hirschfield, FRCP, PhD, Lily and Terry Horner Chair in autoimmune liver disease at the University of Toronto, said in a press release.

Although first-line therapy with ursodeoxycholic acid has been shown to improve transplant-free survival in PBC, nearly 40% of patients treated with ursodeoxycholic acid experience an inadequate response, with increased risk for hepatic complications and poor outcomes. Obeticholic acid had been given accelerated FDA approval for inadequate responders in 2016, with full approval contingent on establishing benefit for clinical outcomes, including hepatic decompensation, liver transplant and mortality.

Using data from the POISE trial, Hirschfield and colleagues compared results of patients treated with OCA from the double-blind and open label extension periods (n = 209) with those generated by “real-world controls” not treated with OCA from the Global PBC (n = 1,381) and UK PBC (n = 2,135) registry studies.

Baseline characteristics reflected a predominantly female epidemiology of PBC with most diagnosed between 50 and 60 years of age and receiving ursodeoxycholic acid therapy between 900 mg/day and 1,000 mg/day for 3.5 to 4 years at index. The primary outcome was time to first occurrence of liver transplant or death.

Over 6 years of follow-up, researchers observed liver transplantation or death among 2.4% of patients from the POISE cohort, 10% of patients from the Global PBC cohort and 13.2% of patients from the UK PBC cohort.

Pre-specified propensity scoring yielded hazard ratios of 0.29 (95% CI, 0.1-0.83) for POISE vs. Global PBC and 0.3 (95% CI, 0.12-0.75) for POISE vs. UK PBC; researchers noted these results indicated patients treated with OCA in a trial setting had a “significantly greater transplant-free survival than patients in either external control group.”

Further analysis revealed 16 incidences of death, liver transplant or hepatic decompensation among 209 patients in the POISE cohort vs. 212 incidences among 1,381 patients in the Global PBC cohort (HR = 0.42; 95% CI, 0.21-0.85).

“Given the known challenges associated with conducting blinded, placebo-controlled trials when the treatment has been approved and is available, this study provides evidence that a well-matched external comparator group can be a credible, alternate approach to evaluating clinical efficacy,” Michelle Berrey, MD, MPH, president of research and development and chief medical officer at Intercept Pharmaceuticals, said in the release. “We look forward to further leveraging real-world databases to continue generating insights on the clinical benefit of Ocaliva (OCA, Intercept) in PBC.”