S2399 Second Line Therapy (2LT) for Primary Biliary Cholangitis (PBC) Is Underutilized in Patients With Advanced Fibrosis and Suboptimal Response to Ursodeoxycholic Acid (UDCA)

Introduction: Primary biliary cholangitis (PBC) is a chronic progressive liver disease characterized by the destruction of small bile ducts within the liver. PBC primarily affects older women and is diagnosed by elevated alkaline phosphatase (ALP) levels and positive antimitochondrial autoantibodies (AMA). Ursodeoxycholic acid (UDCA) is the first-line treatment to delay disease progression. However, up to 40% of patients do not respond to UDCA. Second-line therapy (2LT) is approved for those who do not achieve biochemical remission (BR) with UDCA. This study aims to compare individuals with F0-2 fibrosis to those who have advanced fibrosis (F3-4), to evaluate treatment response and utilization of 2LT. Methods: Retrospective analysis of PBC patients followed from January 1, 2019 to January 1, 2025. Data included baseline demographics, ALP before UDCA initiation, and UDCA response defined as Biochemical Remission [BR] (ALP <1.67 × ULN) and not in remission [NR] (ALP >1.67 × ULN or ALP >175). For those without BR, initiation of 2LT was recorded. Results: Sixty-five patients with PBC were identified after excluding those lost to follow-up (2), incomplete data (6), and death (2). Average age of 65 years, 92% woman, 93% White, 5% Black, 2% other. Thirty-seven (57%) patients had F0-2 fibrosis and 28 (43%) had advanced fibrosis (F3-4). F0-F2 patients were younger (average age 62 vs 69), with lower baseline total bilirubin (TB) 0.5 mg/dL (0.08-1) vs 1.0 mg/dL (0.3-4.2) but baseline ALP 155 (39-659) vs 162 (69-425) was similar. There were 28 in BR and 9 (24%) NR in the F0-F2 group. Twenty-five on 1LT [20 (80%) BR], 9 on 2LT [5 (55%) BR], and 3 on no therapy (100%) BR. Forty-four percent (4/9) of NR F0-2 patients were on 2LT. Nineteen F3-4 patients were in BR and 9 (32%) were NR. Nineteen were on 1LT [13 (68%) BR], 5 on 2LT [3 (60%) BR], 4 on no therapy [3 (75%) BR]. Twenty-two percent (2/9) F3-4 NR patients received 2LT. Two patients not on 2LT had decompensated cirrhosis. Conclusion: Biochemical remission is associated with better long-term outcomes. F3-4 patients are less likely to achieve BR with URSO and less likely to receive 2LT. Even after excluding patients with decompensated cirrhosis, 2LT is underutilized in those with more advanced disease.