LAUSR

Introduction In patients with primary biliary cholangitis (PBC), bilirubin (BILI) is a recognised marker of disease progression and a strong predictor of survival. Recently, the Global PBC Study Group reported risk with elevated BILI extends into the normal range with a cutoff of 0.67x ULN identifying patients at risk. Obeticholic acid (OCA) is indicated for treatment of PBC in patients with inadequate response or intolerability to ursodeoxycholic acid. This retrospective analysis aimed to evaluate the effect of OCA on BILI in this patient subpopulation. Methods OCA has been evaluated in patients with PBC in one 12 month (mo) Phase 3 double-blind (DB) placebo (PBO)-controlled trial (POISE) and two 3-mo Phase 2 PBO-controlled trials (201 and 202). Patients were eligible to continue treatment in open-label extensions (OLE) with all patients receiving OCA. Patients from the Phase 2 and 3 trials with baseline (BL) total BILI (TBILI) ≥0.67 x ULN were evaluated for change in TBILI over 12 mo in the following manner: 1) DB comparison of OCA vs PBO at 12 mo in POISE and 2) DB +OLE OCA use totaling 1 year of treatment (POISE randomised to PBO, evaluated at 12 mo OLE; Phase 2 randomised to OCA for 3 mo, evaluated at 9 mo OLE; and Phase 2 randomised to PBO, evaluated at 12 mo OLE). Results The analysis included patients with TBILI ≥0.67 x ULN at their OCA BL: POISE, n=51; 201, n=7; and 202, n=7. In patients with BL TBILI ≥0.67 x ULN, TBILI increased after 12 mo of PBO treatment, and decreased after 12 mo of OCA (table 1). In the DB phase of POISE, of the 7 PBO and 9 OCA patients with abnormal TBILI at BL, 14% of PBO and 78% of OCA patients attained normal TBILI levels after 12 mo. Further, of 10 PBO and 20 OCA patients with normal TBILI at BL, 60% of PBO and 15% of OCA patients worsened to abnormal TBILI after 12 mo. Conclusions Patients treated with OCA had a trend toward reduction of TBILI compared with those treated with PBO. These data suggest that OCA may reduce progression of patients with more advanced liver disease.Abstract PWE-080 Table 1 12 Mo Treatment PBO OCA Phase DB OLE Study POISE 201 202 POISE Dose (mg) - 5–10 10 10 or 50 10, 25, or 50 5 to 10 n 17 15 14 7 7 17 Mean (SD) change from BL in TBILI (µmol/L) 2.6 (6.5) −3.3 (3.6) −4.0 (7.8) −8.1 (6.4) −10.1 (8.1) −1.6 (7.9) OCA BL- OCA-randomised patients: if time from last DB visit to first OLE visit ≤30 days, mean of evaluations prior to first DB dose is used; if >30 days, last assessment prior to first dose in OLE is used; the initial OLE visit is included as a BL evaluation - PBO-randomised patients: last assessment prior to first dose in OLE is used; initial OLE visit is included as a baseline evaluation