P33 Outcomes with triple therapy (ursodeoxycholic acid, fibrate and obeticholic acid) for treatment of high-risk primary biliary cholangitis

<h3>Aim</h3> Escalation of therapy in high-risk patients (stratified according to biochemistry) with primary biliary cholangitis (PBC) is well-established. An inadequate response to 1st-line therapy with ursodeoxycholic acid (UDCA) is commonly defined as alkaline phosphatase (ALP)&gt;1.67xULN after 1-year of treatment. Obeticholic acid (OCA) is the mainstay of licensed 2nd-line therapy in the UK with fibrates used as an alternative, off-licence treatment (particularly in patients with itch). All 3 can be combined for the small proportion with inadequate response to dual therapy. We have reviewed our single centre experience of triple therapy for PBC. <h3>Method</h3> This retrospective cohort study included patients identified from pre-existing databases to assess demographics, biochemistry and adverse events up to month 24 of triple therapy. <h3>Results</h3> All 27 patients received UDCA as 1st-line therapy (mean age at diagnosis 49 years (SD±7.7); 24 (88.9%) female. ALP response rates are summarised in table 1. There was no statistically significant difference in ALP reduction between the two treatment groups at any time point. A fibrate was added 1st (FIB-OCA) in 13 (48.1%) (median baseline ALP 220 (IQR 75)). Following addition of OCA, there was sustained ALP decrease from baseline of 26–39.3% between month 6 to 24 of treatment. Median baseline alanine transaminase (ALT) was 46 (IQR 50). Percentage ALT reduction from baseline was 26% at months 6 and 12 and 19% at month 24. 3 (23.1%) patients stopped OCA (2 itch and 1 non-response). 14 (51.9%) patients had OCA prior to addition of fibrate (OCA-FIB) (median baseline ALP 244.5 (IQR 157.5)), leading to a sustained ALP reduction of 34.6–38.1% from month 6 to 24. Median baseline ALT was 44 (IQR 49) with 29.5% reduction at 12 months and 22.7% at 24 months. 1 patient required dose reduction of bezafibrate due to renal impairment. No patients had to stop treatment. <h3>Discussion</h3> Sustained reduction in ALP occurred in both groups, irrespective of the order of treatment escalation. 75% achieved normal ALP in the FIB-OCA group but nearly ¼ of patients stopped OCA in this group. Over 60% in both groups had ALP&gt;1.67xULN prior to triple therapy. The others received triple therapy with the target of normalisation of ALP. Percentage achievement of ALP &lt;1.67xULN and normalisation of ALP were similar in both groups, with no statistically significant difference between the groups at any time point. The use of triple therapy is effective in achieving the ultimate goal of PBC treatment with ALP normalisation.