P3491 - Evaluation of Aspartate Aminotransferase to Platelet Ratio Index and Fibrosis-4 Index Stabilization in the Phase 3 POISE Trial of Obeticholic Acid for the Treatment of Primary Biliary Cholangitis

Alan Bonder, ¹, Darren Wheeler, PhD², Jing Li, PhD², Christopher Gasink, MD², Robert G. Gish, MD^3
1Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; ²Intercept Pharmaceuticals, Inc., Morristown, NJ; ³Robert G. Gish Consultants, LLC, San Diego, CA

Introduction: Fibrosis progression prediction using aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) index has not been validated in patients (pts) with primary biliary cholangitis (PBC). A post hoc analysis of the impact of obeticholic acid (OCA), an approved treatment for PBC, on APRI and FIB-4 was performed in pts from POISE, a 12-month (M), randomized, double-blind (DB), placebo (PBO)-controlled phase 3 study and 5-year open-label extension (OLE).

Methods: In the DB phase of POISE, pts were randomized to PBO (n=73), OCA 5–10 mg (n=70), or OCA 10 mg (n=73). During the OLE, all pts were initially treated with OCA 5 mg daily for 3M, after which the dose could be titrated based on response and tolerability. APRI and FIB-4 were calculated at baseline (BL) and each year during the DB phase and OLE in pts with low vs high BL APRI (< 0.5 vs ≥ 1.5) or FIB-4 (< 1.45 vs ≥ 2.67). Summary statistics for APRI and FIB-4 for OCA-treated pts (≤ 10 mg) were generated starting from OCA initiation.

Results: In the DB phase, mean APRI scores increased in PBO-pts with low or high APRI at BL (0.37 at BL vs 0.38 at M12 and 2.76 at BL vs 3.37 at M12, respectively) but decreased in OCA 5–10 mg-pts with low or high APRI at BL (0.37 at BL vs 0.32 at M12 and 2.50 at BL vs 2.16 at M12, respectively). Mean FIB-4 increased in PBO-pts with low or high FIB-4 at BL (1.04 at BL vs 1.22 at M12 and 4.62 at BL vs 5.43 at M12, respectively). FIB-4 values in OCA 5–10 mg were lower than PBO at the end of the DB phase for pts with low or high FIB-4 at BL (1.08 at BL vs 1.04 at M12 and 4.20 at BL vs 4.60 at M12, respectively). In the OLE, mean APRI decreased in OCA-treated pts with low or high APRI at BL (0.39 at BL vs. 0.36 at M60 and 2.74 at BL vs 2.48 at M60, respectively; Figure 1A). In OCA-treated pts with low FIB-4 at BL, mean FIB-4 values were 1.06 at BL and 1.20 at M60, and in pts with high FIB-4 at BL, mean FIB-4 values were 4.45 at BL and 5.65 at M60 (Figure 1B). The sample size for APRI and FIB-4 substantially decreased at M72, limiting interpretability of the data at this time point.

Discussion: The data suggest that OCA prevents or mitigates worsening of fibrosis in pts without risk or at low risk at BL and stabilizes fibrosis in pts with moderate to severe fibrosis at BL. The findings imply that it may be beneficial to treat pts with OCA early before PBC progresses and risk of fibrosis increases.



Disclosures:


Alan Bonder, ¹, Darren Wheeler, PhD², Jing Li, PhD², Christopher Gasink, MD², Robert G. Gish, MD³. P3491 - Evaluation of Aspartate Aminotransferase to Platelet Ratio Index and Fibrosis-4 Index Stabilization in the Phase 3 POISE Trial of Obeticholic Acid for the Treatment of Primary Biliary Cholangitis, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.