P100 Evaluation of response to obeticholic acid in primary biliary cholangitis treatment – single centre retrospective observational study

<h3>Introduction</h3> Obeticholic acid (OCA) is a licensed second-line therapy approved for use by NHS England for patients with primary biliary cholangitis (PBC) that have inadequate response or intolerance to ursodeoxycholic acid. However, response rates to obeticholic acid were 46% in the POISE trial and thus, patients require further treatment options. Several therapies are undergoing phase three trials such as elafibranor and seladelpar, which show promising data as future treatment options. We aimed to evaluate the safety and efficacy of OCA in our local cohort in order to identify the number of patients who would be eligible for future second line therapies. <h3>Methods</h3> A retrospective study over a five year follow up period was conducted in a large tertiary hepatology unit in London, UK. All patients who were referred to the PBC MDM for second-line treatment of PBC between November 2017 and November 2019 with complete blood tests were included. The primary endpoint was ALP &lt; 1.67 x ULN at month 12 (according to POISE criteria), normal levels of alkaline phosphatase (ALP) &lt; 130U/L and bilirubin &lt; 21μmol/L. We also assessed for safety and tolerability of OCA. <h3>Results</h3> 113 patients were included in the study. 49 patients (43.4%) were referred from the hub hospital and 64 patients (56.6%) were referred from spoke sites.¹ The median age was 57 years, and 101 patients (89.4%) were female. 67 patients (59.3%) were approved for obeticholic acid, but 14 patients’ (20.9%) care were transferred back to the referring site following local prescribing approval. Of the remaining 53 patients, 22 patients (41.5%) remain on OCA treatment (18 patients as second-line therapy and 4 patients as monotherapy), and 13 patients (24.5%) discontinued OCA treatment due to intolerances, mostly pruritus. Response rates were 13 patients (59%) according to POISE criteria.² At the time of most recent blood tests, patients received a median of 56 months of OCA treatment. Of the 22 patients, only 3 patients (13.6%) achieved a normal ALP (2 patients as second-line therapy and 1 patient as monotherapy) and 21 patients (95.5%) had normal bilirubin levels. <h3>Conclusion</h3> Although 59% reached POISE response criteria, most of the patients treated with OCA did not achieve normalisaton of ALP. As treatment paradigms change for PBC, this study highlights that a high proportion of patients should be considered for further treatment options. <h3>References</h3> Francisco A, Shah S, Heneghan M<i>, et al</i>. P30 Is a virtual pharmacy-led hub and spoke model effective in managing primary biliary cholangitis with obeticholic acid? <i>Gut</i> 2020;<b>69</b>:A21. Doi: https://doi.org/10.1136/gutjnl-2023-BASL.118 Nevens F, <i>et al</i>. A placebo-controlled trial of obeticholic acid in primary biliary cholangitis. <i>The New England Journal of Medicine</i> 2016;<b>375</b>:631–643. Doi: https://doi.org/10.1056/nejmoa1509840