Surrogate Endpoints for Optimal Therapeutic Response to UDCA in Primary Biliary Cholangitis

Abstract

Background: Ursodeoxycholic acid (UDCA) is the standard treatment for primary biliary cholangitis (PBC), as it can delay histological progression, improve long-term outcome and is extremely safe and well tolerated. However, UDCA is not always sufficient and the prognosis of patients inadequately responding to treatment is worse compared with the general population. Reliable identification of so-called non-responders is of key importance, not only for selecting patients who could benefit from additional, second-line therapy, but also for identifying those individuals who are at low risk of developing end-stage disease and in whom UDCA mono-therapy can be safely continued. Several laboratory surrogate endpoints for the long-term response to UDCA have been proposed, including the Barcelona, Paris, Toronto and Rotterdam criteria. All these criteria have limitations and the superiority of one over the other has not been firmly established. Key Messages: Recently the Global PBC Study Group developed a new prognostic tool by studying a large, representative and multinational cohort of 4,119 UDCA-treated patients. In a random sample of 2,488 cases, a risk score - the GLOBE score - was developed, predictive of transplantation-free survival. This risk score comprises age, and bilirubin, albumin, alkaline phosphatase and platelet count obtained after 1 year therapy, and has a performance (C statistic 0.81, 95% CI 0.79-0.83) that is markedly better than that of previously proposed response criteria. Comparable performance was found in an independent validation cohort of 1,631 cases (C statistic 0.82, 95% CI 0.79-0.84). A web app will allow the easy use of the score in clinical practice.