Efficacy and Safety of Obeticholic Acid Therapy in Primary Biliary Cholangitis
Introduction
Primary biliary cholangitis (PBC), an autoimmune liver disease, if under-treated, can lead to fibrosis progression culminating into end stage liver disease. Ursodeoxycholic acid (UDCA) has been used as the first-line therapy in PBC. However, it may not be effective in all the patients. In 2016, obeticholic acid (OCA) received approval as the second-line treatment for patients with an inadequate response or intolerance to UDCA. Results from a randomized controlled trial, POISE and its open-label extension showed significant reduction of alkaline phosphatase (ALP) and stabilization of total bilirubin with 48 months of OCA treatment. However, there is paucity of real-world data on OCA.
Aim
This study assessed the efficacy, safety and tolerability of OCA under real-world conditions in a large cohort of patients with PBC.
Method
Study Design
- Retrospective study of data within the Italian PBC registry, an on-going, non-interventional, multicenter, observational cohort study
Treatment Strategy
- Patients recruited into the Italian PBC Registry, an on-going, multicentre, observational cohort study, diagnosed with PBC and consecutively starting OCA treatment were screened
- The overall cohort (OC) comprised patients who received at least 1 dose of OCA and had at least 12 months of follow-up
- The Treatment Completer Cohort (TCC) was defined as all patients who completed the treatment period of 6 or 12 months for the analysis at 6 or 12 months, respectively.
End Points
Primary End Point
- Biochemical response at 6 and 12 months of OCA therapy using the Poise definition of biochemical response: alkaline phosphatase (ALP) <1.67/upper limit of normal (ULN) with a reduction of ≥15% from baseline and a normal total bilirubin level, as applied in the registrative trial of OCA (Poise criteria).
Secondary End Points
- Biochemical response at 6 and 12 months of OCA therapy according to normal range criteria: defined as normal levels of ALP, alanine aminotransferase (ALT) and bilirubin
- Adverse events (AEs)
Results
- A total of 191 patients with at least 12 months of follow-up were analysed.
- Characteristics of cohort were as follows
- Median age of 57 years
- 94% females
- Cirrhosis in 32%
- 15% had histologically proven overlap with autoimmune hepatitis (PBC-AIH).
- 25% had a history of pruritus
- The response rates in the OC and TCC at 6 and 12 months according to the Poise and normal range criteria are depicted in Figure 1.
- At 6 and 12 months, there were significant median reductions of ALP (-24.6% and -32.3%), ALT (-30% and -31.4%), and bilirubin (-3.9% and -11.2%) respectively
- Response rates were 42.9% according to Poise criteria, and 11% by normal range criteria.
- At 12 months, patients with cirrhosis had lower response than patients without cirrhosis (29.5% vs. 49.2%, p = 0.01), owing to a higher rate of OCA discontinuation (30% vs. 12%, p = 0.004), although with similar ALP reduction (29.4% vs. 34%, p = 0.53).
- Patients with overlap PBC-AIH had a similar response to pure PBC (46.4% vs. 42.3%, p = 0.68)
- The reduction of ALT levels at 6 months was significantly higher in PBC-AIH overlap patients as compared to pure PBC patients (-38% vs. -29%, p = 0.04).
- OCA therapy was discontinued prematurely in 17% due to AEs (n=33), of whom 11 experienced serious AEs
- Pruritus was the most common AE seen in 27.3% and caused treatment discontinuation in 66%.
Conclusions
- The results obtained in the Poise trial on efficacy, safety and tolerability of obeticholic acid (OCA) can be reproduced in real-world conditions in patients with primary biliary cholangitis (PBC).
- Patients with cirrhosis had lower tolerability and might need optimization of pruritus control before starting OCA and during the treatment.
- OCA therapy might benefit patients with overlap PBC-autoimmune hepatitis (PBC-AIH), who demonstrated higher ALT reduction at 6 months compared with patients with pure PBC.
JHEP Rep. 2021 Jan 27;3(2):100248. Doi: 10.1016/j.jhepr.2021.100248.
