Obeticholic acid 5mg tablets

Obeticholic acid (OCA), a potent farnesoid X receptor agonist, was studied as monotherapy in an international, randomized, double‐blind, placebo‐controlled phase 2 study in patients with primary biliary cholangitis who were then followed for up to 6 years. The goals of the study were to assess the benefit of OCA in the absence of ursodeoxycholic acid, which is relevant for patients who are intolerant of ursodeoxycholic acid and at higher risk of disease progression. Patients were randomized and dosed with placebo (n = 23), OCA 10 mg (n = 20), or OCA 50 mg (n = 16) given as monotherapy once daily for 3 months (1 randomized patient withdrew prior to dosing). The primary endpoint was the percent change in alkaline phosphatase from baseline to the end of the double‐blind phase of the study. Secondary and exploratory endpoints included change from baseline to month 3/early termination in markers of cholestasis, hepatocellular injury, and farnesoid X receptor activation. Efficacy and safety continue to be monitored through an ongoing 6‐year open‐label extension (N = 28). Alkaline phosphatase was reduced in both OCA groups (median% [Q1, Q3], OCA 10 mg −53.9% [−62.5, −29.3], OCA 50 mg −37.2% [−54.8, −24.6]) compared to placebo (−0.8% [−6.4, 8.7]; P < 0.0001) at the end of the study, with similar reductions observed through 6 years of open‐label extension treatment. OCA improved many secondary and exploratory endpoints (including γ‐glutamyl transpeptidase, alanine aminotransferase, conjugated bilirubin, and immunoglobulin M). Pruritus was the most common adverse event; 15% (OCA 10 mg) and 38% (OCA 50 mg) discontinued due to pruritus. Conclusion: OCA monotherapy significantly improved alkaline phosphatase and other biochemical markers predictive of improved long‐term clinical outcomes. Pruritus increased dose‐dependently with OCA treatment. Biochemical improvements were observed through 6 years of open‐label extension treatment. (Hepatology 2018;67:1890‐1902).

Abstract licence: CC BY-NC-ND 4.0

Abstract Background Metabolic dysfunction-Associated Fatty Liver Disease (MAFLD) is a metabolic liver disorder characterised by excessive fat buildup in the liver, closely linked with obesity, diabetes, and lifestyle factors, with potential progression into advanced liver disease. This review aims to evaluate the therapeutic role of Sodium–glucose cotransporter 2 inhibitors (SGLT2i) and Obeticholic acid (OCA) in MAFLD-related fibrosis. Recently, the Food and Drug Administration (FDA) approved Resmetirom and Semaglutide for Metabolic dysfunction-Associated Steatohepatitis (MASH) with moderate to advanced fibrosis. OCA is currently under research for its efficacy in treating MASH. At the same time, SGLT2i are being investigated in various phases for MAFLD, though large-scale Phase III trials are still forthcoming. Methods A systematic review was conducted, identifying a total of 5,253 articles from PubMed, Embase, Google Scholar and Web of Science. Only peer-reviewed, full-text RCTs were included and assessed for bias using RoB 2. After a strict quality assessment, data from 16 studies were gathered and included. The certainty of Evidence was evaluated for every outcome using the GRADE approach. Results Both OCA and SGLT2i lead to histological improvement and improve liver enzyme levels. However, MASH resolution was more prominent with OCA, though it was attributed to adverse effects such as dyslipidemia and pruritus. Conclusion Despite the potential of both drug classes, this parallel evidence synthesis emphasises the necessity of additional research to determine their relative safety and efficacy in MAFLD.

Abstract licence: CC BY 4.0

Background: Although the efficacy of ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) for primary biliary cholangitis (PBC) has been suggested by small trials, a meta-analysis to summarize the evidence has not yet been carried out. The aim of this study was to evaluate the clinical outcomes of the combination therapy of UDCA and OCA compared with UDCA monotherapy in patients with PBC. Methods and materials: We searched the PubMed, EMBASE, the web of science, and the Cochrane Library databases for English-language studies published before September 2018. Studies were included if they were randomized controlled trials (RCTs) and reported relative risk (RR) estimates with 95% confidence intervals (CIs) or related data for the clinical outcomes of different therapies in patients with PBC. Results: Of the 1169 titles identified, two studies meeting the inclusion criteria were included in the meta-analysis. Approximately 222 patients with PBC were included in this analysis. The results of this study indicated that combination therapy was significantly superior to monotherapy in reducing serum alanine transaminase (mean difference: –15.63 IU/L; 95% CI, –21.59 to –9.68), aspartate transaminase (mean difference: –6.63 IU/L; 95% CI, –11.03 to –2.24), gamma-glutamyl transpeptidase (mean difference: –131.30 IU/L; 95% CI, –177.52 to –85.08), and C-reactive protein (mean difference = –1.17 mg/L; 95% CI, –2.19 to –0.14), but NS in improving primary endpoints of alkaline phosphatase level with 15.0% reduction from baseline, and equal or higher than the upper limit of normal serum total bilirubin (RR = 2.75; 95% CI, 0.43–17.68), conjugated bilirubin (mean difference = –0.06 mg/dL; 95% CI, –0.28 to 0.15), IgM (mean difference = –41.18 mg/dL; 95% CI, –244.45 to 162.09), and adverse events (P > 0.05). Conclusion: This meta-analysis demonstrated that combination therapy with UDCA and OCA provided satisfactory clinical outcomes, which may be a promising alternative for patients with PBC who had an inadequate response to UDCA therapy. Therefore, high-quality RCTs on the safety and efficacy of the combination therapy of UDCA and OCA compared with UDCA monotherapy in patients with PBC should be performed in the future.

Abstract licence: CC BY-NC-ND 4.0