Primary Biliary Cholangitis
Conditions
Keywords
Primary Biliary Cholangitis, Primary Biliary Cirrhosis, PBC, Hepatic Impairment, Liver
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.
Interventions
None listed
Sponsors
Target RWE
Syneos Health
Komodo Health, Inc.
Intercept Pharmaceuticals
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
This study was conducted in the United States (US) and data was analyzed from Komodo Health claims database between 01 Jun 2015 to 31 Dec 2021.
Pre-assignment details
Participants were included if, between 01Jun2015 and 31Dec2021, they met criteria for PBC diagnosis: At least 1 inpatient claim with an associated PBC International Classification of Diseases (ICD)-10 code, or at least 2 outpatient claims separated by \>1 day with a PBC ICD-9 or ICD-10 code. Patient records (indexes) were selected from a healthcare database. The unit of analysis were indexes, not participants. Analysis was conducted using weighted index methods.
Participants by arm
| Arm | Count |
|---|---|
| OCA-treated PBC participants with a history of UDCA failure (inadequate response, intolerance, or discontinuation) who initiated OCA in the study window were included. | 403 |
| OCA-treated PBC participants with a history of UDCA failure (inadequate response, intolerance, or discontinuation) who initiated OCA in the study window were included. | 403 |
| Non-OCA Treated PBC participants with a history of UDCA failure who were eligible but not treated with OCA for the study. This was a real-world study, and it was conducted in a population of participants selected from a database using weighted index methods. | 4,174 |
| Non-OCA Treated PBC participants with a history of UDCA failure who were eligible but not treated with OCA for the study. This was a real-world study, and it was conducted in a population of participants selected from a database using weighted index methods. | 405 |
| Total | 5,385 |
Baseline characteristics
| Characteristic | Non-OCA Treated | Total | OCA-treated |
|---|---|---|---|
| Age, Continuous | 55.859 Years STANDARD_DEVIATION 12.599 | 56.036 Years STANDARD_DEVIATION 11.638 | 56.213 Years STANDARD_DEVIATION 10.58 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region Midwest | 38 Indexes | 76 Indexes | 38 Indexes |
| Region Northeast | 84 Indexes | 166 Indexes | 82 Indexes |
| Region South | 175 Indexes | 361 Indexes | 186 Indexes |
| Region Territory | 1 Indexes | 1 Indexes | 0 Indexes |
| Region Unknown | 1 Indexes | 1 Indexes | 0 Indexes |
| Region West | 106 Indexes | 203 Indexes | 97 Indexes |
| Sex: Female, Male Female | 369 Indexes | 738 Indexes | 369 Indexes |
| Sex: Female, Male Male | 36 Indexes | 70 Indexes | 34 Indexes |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 12 / 403 | 17 / 405 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
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.
Time frame: Up to 67 months
Population: Weighted index population. The unit of analysis is Indexes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OCA-treated | Risk of the First Event of the Composite Events | 8 Events during the study period |
| Non-OCA Treated | Risk of the First Event of the Composite Events | 32 Events during the study period |
p-value: <0.00195% CI: [0.143, 0.752]Nonparametric bootstrap approach
Secondary
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).
Time frame: Up to 67 months
Population: Weighted index population. The unit of analysis is Indexes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OCA-treated | Risk of Death | 2 Events during the study period |
| Non-OCA Treated | Risk of Death | 9 Events during the study period |
Secondary
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.
Time frame: Up to 67 months
Population: Weighted index population. The unit of analysis is Indexes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OCA-treated | Risk of Hospitalization for Hepatic Decompensation | 6 Events during the study period |
| Non-OCA Treated | Risk of Hospitalization for Hepatic Decompensation | 23 Events during the study period |
Secondary
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.
Time frame: Up to 67 months
Population: Weighted index population. The unit of analysis is Indexes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OCA-treated | Risk of Liver Transplantation | 2 Events during the study period |
| Non-OCA Treated | Risk of Liver Transplantation | 12 Events during the study period |