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

Completed

Brief Summary: 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.

Recruitment & Eligibility

Inclusion Criteria

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

Key

Exclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
OCA Treatment Group	Obeticholic Acid 5 MG	PBC patients with a history of inadequate response or intolerance to UDCA who initiated OCA in the study window (01 Jun 2015 to 31 Dec 2021)
OCA Treatment Group	Obeticholic Acid 10 MG	PBC patients with a history of inadequate response or intolerance to UDCA who initiated OCA in the study window (01 Jun 2015 to 31 Dec 2021)

Primary Outcome Measures

Name	Time	Method
Risk of the First Event of the Composite Events	Up to 67 months	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.

Secondary Outcome Measures

Name	Time	Method
Risk of Death	Up to 67 months	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).
Risk of Liver Transplantation	Up to 67 months	The primary source for liver transplant was the Organ Transplant Network (OPTN) transplant registry. Risk is presented using the number of liver transplantation.
Risk of Hospitalization for Hepatic Decompensation	Up to 67 months	The primary source for hospitalization for hepatic decompensation were Komodo Health claims. Risk is presented using the number of hospitalization for hepatic decompensation.