P3450 - Obeticholic Acid Normalizes Inflammatory Biomarkers in Patients With Primary Biliary Cholangitis

Tenita Foston, FNP¹, David E. Jones, PhD², Christopher L. Bowlus, MD³, Arash Thranian, PhD, MBA¹, Mary Erickson, PhD¹, Jing Li, PhD¹, Christopher Gasink, MD¹, Robert G. Gish, MD^4
1Intercept Pharmaceuticals, Inc., Morristown, NJ; ²Newcastle University, Newcastle upon Tyne, England, United Kingdom; ³University of California Davis Health, Sacramento, CA; ⁴Robert G. Gish Consultants, LLC, San Diego, CA

Introduction: Primary biliary cholangitis (PBC) is characterized by chronic liver inflammation and progressive bile duct destruction. Obeticholic acid (OCA), a farnesoid X receptor agonist, received accelerated approval based on the phase 3 POISE study. We evaluated the impact of OCA on normalizing inflammatory and immune biomarkers in POISE patients (pts).

Methods: Pts with PBC who could not tolerate or had an incomplete response to ursodeoxycholic acid were randomized 1:1:1 to receive PBO, OCA titration (OCA 5 mg with the option to titrate to 10 mg after 6 months), or OCA 10 mg for 12 months. Biomarker levels (tumor necrosis factor α [TNFα], high-sensitivity C-reactive protein [hsCRP], and immunoglobulin M [IgM]) were measured at baseline (BL) and month 12. Normalization was defined as ≤ 8.1 pg/mL for TNFα, ≤ 3 mg/L for hsCRP, and ≤ 2.3 g/L for IgM. The association between treatment and normalization was assessed using Cochran-Mantel-Haenszel test, and the median difference was compared using the Wilcoxon rank-sum test.

Results: In the full intent-to-treat population, median BL levels of TNFα were 11.7, 10.1, and 10.8 pg/mL for PBO, OCA titration, and OCA 10 mg, respectively, and median change from BL at month 12 was 1.2, 0.8, and -0.2 pg/mL (p < 0.01 for OCA 10 mg vs PBO; Fig. 1A). Among pts with TNFα > 8.1 pg/mL at BL (79%), 3% (2/58) on PBO, 23% (10/43) on OCA titration, and 14% (7/49) on OCA 10 mg normalized at month 12 (p < 0.05 for both vs PBO). Median BL hsCRP levels were 3.3, 3.3, and 3.1 mg/L for PBO, OCA titration, and OCA 10 mg, respectively, with median change from BL at month 12 of 0.4, -0.5, and -0.6 mg/L (p < 0.001 for both vs PBO; Fig. 1B). Among pts with elevated hsCRP at BL (53%), 6% (2/34) on PBO, 19% (6/32) on OCA titration, and 39% (13/33) on OCA 10 mg attained ≤ 3 mg/L at month 12 (p = 0.1 and p < 0.001 vs PBO, respectively). Median BL levels of IgM were 4.5, 3.7, and 3.5 g/L for PBO, OCA titration, and OCA 10 mg, respectively, with median change from BL at Month 12 of -0.3, -0.7, and -1.0 g/L (p < 0.001 for both vs PBO; Fig. 1C). Of pts with high IgM at BL (77%), 0% (0/55) on PBO, 15% (6/41) on OCA titration, and 27% (13/48) on OCA 10 mg normalized IgM at month 12 (p < 0.01 for both vs PBO).

Discussion: OCA significantly increased the proportion of pts achieving normalization of the inflammatory biomarkers TNFα, hsCRP, and IgM, the latter of which is associated with better clinical outcomes. These findings support OCA's efficacy in treating the autoimmune aspects of PBC.



Disclosures:


Tenita Foston, FNP¹, David E. Jones, PhD², Christopher L. Bowlus, MD³, Arash Thranian, PhD, MBA¹, Mary Erickson, PhD¹, Jing Li, PhD¹, Christopher Gasink, MD¹, Robert G. Gish, MD⁴. P3450 - Obeticholic Acid Normalizes Inflammatory Biomarkers in Patients With Primary Biliary Cholangitis, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.