Baseline Characteristics and Risk Profiles of 1111 Patients With Primary Biliary Cholangitis (PBC) in Need of Second-Line Therapy

Up to 40% of patients receiving first-line ursodeoxycholic acid (UDCA) for PBC have an ALP≥1.67×ULN and progress. We examined patients who screen failed due to ALP<1.67×ULN in 4 seladelpar clinical trials (2015–2022); 1111 patients with PBC were screened after UDCA treatment≥12 months or UDCA intolerance. ALP≥1.67×ULN was required for enrollment. Baseline characteristics and risk profiles of enrolled patients (EN, ALP≥1.67×ULN) and screen failures (SF, ALP≥ULN, but<1.67×ULN) were compared. We stratified using proportions with Enhanced Liver Fibrosis (ELF) values≥10.0 or bilirubin>0.6×ULN. The relationship of ELF and liver stiffness was confirmed when available. Screened patients were predominantly female (94%) with mean (SD) age of 57±9.5 years. Studies enrolled 54% of screened patients (n=603; EN cohort) with PBC duration 8±6.5 years and UDCA dose 15±3.9 mg/kg/day (92% on UDCA). Overall, 26% of patients (n=284) screen failed due to ALP>ULN but<1.67×ULN (SF cohort). Differences in baseline ALP, GGT, and ALT were observed between cohorts. Higher-risk bilirubin levels were present in 51.1% and 42.0% of EN and SF cohorts, respectively. Elevated risk based on ELF was identified in 43.2% of EN and 27.2% of SF cohorts. Liver stiffness was assessed in 66% of EN patients; mean liver stiffness of 9.7 kPa correlated with ELF (r=0.50, P<0.001). Thus, patients with ALP≥ULN, but<1.67×ULN, often have risk factors for disease progression and should be assessed for second-line therapies.

Publication History

Article published online:
20 January 2025