Misclassification of UDCA treatment response in patients with primary biliary cholangitis (PBC) in the real-world...

Treatment response of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) is assessed after 12 months by Paris II criteria. In the German PBC registry, individuals were stratified into adequate and inadequate Paris II responders. We analyzed the concordance between clinical judgement and formal Paris II classification.

Physician-assessed UDCA treatment response was compared to formal Paris II criteria (alkaline phosphatase (ALP) or aspartate-aminotransferase (AST) >1.5 x ULN or bilirubin >1 mg/dL).

10/130 (8%) cases were misclassified as inadequate UDCA responders, 44/253 (17%) as adequate responders despite not meeting Paris II criteria. Incorrectly classified responders occurred in 26% versus 13% of individuals at secondary and tertiary centers (p = 0.0141). At secondary centers, 86% of misclassified responders had ALP >1.5 × ULN and 5% had bilirubin >1 mg/dL, compared with 32% and 27% at tertiary centers. ALP levels >1.5 x ULN occurred significantly more often at secondary centers (p = 0.0005). At secondary centers, ALP levels at diagnosis were higher in misclassified versus correctly classified responders (3.6 ± 3.0 x ULN vs. 1.7 ± 0.9 x ULN, p < 0.001) and remained higher after 12 months of therapy (2.3 ± 1.2 vs. 0.9 ± 0.3 × ULN, p < 0.001).

Clinical judgement and Paris II classification differ in 20% of patients. Higher baseline ALP levels and kinetics may lead to misclassification. This may result in withholding of second line treatments in these patients.