Clinical application of the GLOBE and United Kingdom‐primary biliary cholangitis risk scores in a trial cohort of patients with primary biliary cholangitis

Abstract

The GLOBAL Primary Biliary Cholangitis (PBC) Study Group and United Kingdom‐PBC (UK‐PBC) Consortium have demonstrated that dichotomous response criteria are not as accurate as continuous equations at predicting mortality or liver transplantation in PBC. The aim of this analysis was to assess the clinical utility of the GLOBE and UK‐PBC risk scores using data from POISE, a phase 3 trial investigating obeticholic acid (OCA) in patients with PBC. Data (N = 216) at baseline and month 12 were used to calculate the GLOBE and UK‐PBC risk scores to assess the projected change in risk with OCA versus placebo. Additionally, the benefit of OCA was assessed in patients not meeting the POISE primary endpoint. Both the GLOBE and UK‐PBC risk scores predicted a significant reduction in long‐term risk of death and liver transplantation after OCA treatment (P < 0.0001). The differences in the relative risk reduction from baseline in the 10‐year event risk after 1 year for OCA 10 mg versus placebo was 26% (GLOBE) and 37% (UK‐PBC). The scores also predicted a significantly decreased risk in patients treated with OCA who did not meet POISE response criteria after 1 year of treatment compared to an increased risk with placebo (P < 0.0001). Conclusion: This analysis demonstrates the use of the GLOBE and UK‐PBC risk scores to assess risk reduction of a cohort treated with OCA. While validation of this risk reduction in studies with clinical outcomes is needed, this study highlights the potential use of these scores in individualizing risk prediction in PBC both in clinical practice and therapeutic trials. (Hepatology Communications 2018;2:683‐692)

The association of histological progression with biochemical response to ursodeoxycholic acid in primary biliary cholangitis

“…Several studies have validated the ability of Globe and UK-PBC risk scores to predict clinical outcomes in patients with PBC. [41][42][43] Absolute alkaline phosphatase and total bilirubin criteria at 1 year after the UDCA therapy have been used as a more robust predictor of hard endpoints such as liver transplantation or deaths of patients with PBC. 35 More recently, Zhang et al reported that earlier biochemical response to UDCA at 3 or 6 months was devised to identify patients at risk of poor outcomes.…”

Obeticholic acid is associated with improvements in AST-to-platelet ratio index and GLOBE score in patients with primary biliary cholangitis

“… 6 However, it is showing utility with other treatments as well. 14 , 17 A recent publication quantified the long-term benefit of OCA in the POISE trial through an analysis of data from POISE according to GLOBE score and also the United Kingdom-PBC (UK-PBC) score developed by the UK-PBC Consortium. 14 The GLOBE and UK-PBC scores were also used to assess the benefit of bezafibrate in combination with UDCA in a retrospective cohort of patients from the Japan PBC Study Group.…”

“… 14 , 17 A recent publication quantified the long-term benefit of OCA in the POISE trial through an analysis of data from POISE according to GLOBE score and also the United Kingdom-PBC (UK-PBC) score developed by the UK-PBC Consortium. 14 The GLOBE and UK-PBC scores were also used to assess the benefit of bezafibrate in combination with UDCA in a retrospective cohort of patients from the Japan PBC Study Group. 17 Both the GLOBE and UK-PBC scores include ALP and total bilirubin, which have been identified as the most important markers in determining LT-free survival in PBC.…”

“… 6 Following 12 months of OCA treatment, calculation of the GLOBE score using data from the POISE trial indicated a significant reduction in the risk of death or liver transplantation at 5, 10, and 15 years. 14 The combination of both APRI threshold and GLOBE score threshold has demonstrated the ability to stratify patients more accurately than either score alone for predicting the risk of major liver-related complications. 3 …”

Emerging novel treatments for autoimmune liver diseases

“…These easy‐to‐use scores with computer‐aided calculations, allow to continuously quantify the risk for progression over time in a single patient. However, that these scores were solely developed for a patient cohort treated with UDCA monotherapy, and whether these scores based on biochemical responses after 1 year of treatment are also applicable to patients treated with additional drugs such as obeticholic acid (OCA) or bezafibrate should be further validated, although a recent retrospective study suggested that it might be applicable in patient cohorts treated with these drugs . In addition, a UDCA response score able to predict responses to UDCA has been proposed, indicating that higher ALP, higher bilirubin, and lower aminotransferase levels, younger age, longer interval from diagnosis to UDCA treatment, and worsening ALP from diagnosis were associated with a lower probability of UDCA response .…”