Real-World Data Study to Evaluate the Effectiveness of OCA on Hepatic Outcomes in PBC Patients (HEROES PBC)

Replicate Studies Evaluating the Effectiveness of Obeticholic Acid on Hepatic Real-World Outcomes in Patients With Primary Biliary Cholangitis

This is an observational, retrospective cohort study of patients with primary biliary cholangitis (PBC) who failed ursodeoxycholic acid (UDCA) treatment, using a real-world data source, the Komodo Health United States (US) claims database. The study is designed to evaluate the effectiveness of obeticholic acid (OCA). All patients who meet diagnostic criteria for PBC in the database between 01 Jun 2015 and 31 Dec 2021 and who meet all eligibility criteria were considered for this study.

Study Overview

• Status: Completed
• Conditions: Primary Biliary Cholangitis
• Intervention / Treatment: Drug: Obeticholic Acid 5 MG; Drug: Obeticholic Acid 10 MG; Drug: Standard of Care: UDCA

• Study Type: Observational
• Enrollment (Actual): 4577

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92121
      • Intercept Pharmaceuticals, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients who meet diagnostic criteria in each database between 01 Jun 2015 and 31 Dec 2021 and who meet the eligibility criteria were considered for these studies.

Description

Key Inclusion Criteria:

1. Definite or probable PBC diagnosis
2. Inadequate response or intolerance to UDCA
3. Age ≥18 years at the index date
4. Continuous enrollment and evaluable data for at least 12 months before the index date (inclusive)

Key Exclusion Criteria:

1. History or presence of other concomitant liver diseases
2. History of non-skin malignancy or melanoma
3. History of HIV
4. Medical conditions that may cause non-hepatic increases in ALP
5. Patients with laboratory values indicative of hepatic decompensation or significant hepatobiliary injury
6. History of liver transplant
7. Evidence of fenofibrate, or bezafibrate use
8. History or presence of hepatic decompensating events

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
OCA-treated; PBC participants with a history of UDCA failure (inadequate response, intolerance, or discontinuation) who initiated Obeticholic acid (OCA) in the study window.
Non-OCA Treated; PBC participants with a history of UDCA failure who were eligible but not treated with OCA (or off-label fibrates) in the study window.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk of the First Event of the Composite Events	The primary analysis outcome was assessed with hazard ratio (HR) comparing hazard of first event of the composite endpoint among OCA-treated participants and SMR-weighted non-OCA-treated PBC participants indexes. It included all-cause death, liver transplant, hospitalization for hepatic decompensation based on first occurrence of: variceal bleed, ascites (including hepatic hydrothorax and spontaneous bacterial peritonitis) and hepatic encephalopathy. OCA-treated indexes were censored 90 days after OCA discontinuation, or if fibrates were initiated. Control indexes were censored if a participant-initiated OCA therapy, initiated fibrate therapy, reinitiated UDCA for participants who had discontinued UDCA for >6 months, or end of study period (31 Dec 2021), whichever came first. The 2.5th and 97.5th percentile of nonparametric bootstrap samples were used to estimate 95% CI for HR and to perform a test of hypothesis. Risk is presented using the number of composite event and components.	Up to 67 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk of Death	The primary source for death was the Social Security Death Index (SSDI) along with obituary search, which was compared to Komodo Health claims and LabCorp/Quest laboratory data. The secondary objectives were to estimate the effect of OCA treatment versus non-OCA treatment on each component of the composite endpoint, with the same censoring rule applied as in the primary composite endpoint. Risk is presented using the the number of all-cause death within the risk period (prior to censoring).	Up to 67 months
Risk of Liver Transplantation	The primary source for liver transplant was the Organ Transplant Network (OPTN) transplant registry. Risk is presented using the number of liver transplantation.	Up to 67 months
Risk of Hospitalization for Hepatic Decompensation	The primary source for hospitalization for hepatic decompensation were Komodo Health claims. Risk is presented using the number of hospitalization for hepatic decompensation.	Up to 67 months

Other Outcome Measures

Outcome Measure	Time Frame
Time to the first occurrence of all-cause death	Time from index date to first occurrence of all-cause death, assessed up to 67 months.
Time to the first occurrence of liver transplant	Time from index date to first occurrence of liver transplant, assessed up to 67 months.
Time to first occurrence of hospitalization for hepatic decompensation	Time from index date to first occurrence of hospitalization for hepatic decompensation, assessed up to 67 months.

Collaborators and Investigators

• Sponsor: Intercept Pharmaceuticals
• Collaborators: Syneos Health; Target RWE; Komodo Health, Inc.
• Investigators: Study Director: Lynda Szczech, MD, Intercept Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: March 4, 2022
• First Submitted That Met QC Criteria: March 14, 2022
• First Posted (Actual): March 23, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Hepatic Impairment; Liver; Primary Biliary Cholangitis; PBC; Primary Biliary Cirrhosis
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Biliary Tract Diseases; Liver Diseases; Bile Duct Diseases; Fibrosis; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Cholangitis; Liver Cirrhosis, Biliary; Gastrointestinal Agents; Cathartics; Chenodeoxycholic Acid
• Other Study ID Numbers: 747-405

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No