Effectiveness and safety of obeticholic acid in a Southern European multicentre cohort of patients with primary biliary cholangitis and suboptimal response to ursodeoxycholic acid

Abstract

SummaryBackgroundObeticholic acid (OCA) was recently approved as the only on‐label alternative for patients with primary biliary cholangitis (PBC) with intolerance or suboptimal response to ursodeoxycholic acid (UDCA). However, few data are available outside clinical trials.AimTo assess the effectiveness and safety of OCA in a real‐world cohort of patients with non‐effective UDCA therapy.MethodsOpen‐label, prospective, real‐world, multicentre study, enrolling consecutive patients who did not meet Paris II criteria, from 18 institutions in Spain and Portugal. Effectiveness was assessed by the changes in GLOBE and UK‐PBC scores from baseline. POISE and Paris II criteria were evaluated after 12 months of OCA . Liver fibrosis was evaluated by FIB‐4 and AST to platelet ratio index (APRI).ResultsOne hundred and twenty patients were eligible, median time since PBC diagnosis 9.3 (4.0‐13.8) years, 21.7% had cirrhosis, and 26.7% received had previous or concomitant treatment with fibrates. Seventy‐eight patients completed at least 1 year of OCA. The Globe‐PBC score decreased to 0.17 (95% CI 0.05 to 0.28; P = 0.005) and the UK‐PBC score decreased to 0.81 (95% CI −0.19 to 1.80; P = 0.11). There was a significant decrease in alkaline phosphatase of 81.3 U/L (95% CI 42.5 to 120; P < 0.001), ALT 22.1 U/L (95% CI 10.4 to 33.8; P < 0.001) and bilirubin 0.12 mg/dL (95% CI 0 to 0.24; P = 0.044). FIB‐4 and APRI remained stable. According to the POISE criteria, 29.5% (23 out of 78) achieved response. The adverse events rate was 35%; 11.67% discontinued (8.3% due to pruritus).ConclusionsThis study supports data from phase III trials with significant improvement of PBC‐Globe continuous prognostic marker score among OCA‐treated patients with good tolerability.

Ursodeoxycholic Acid Treatment–Induced GLOBE Score Changes Are Associated With Liver Transplantation-Free Survival in Patients With Primary Biliary Cholangitis

“…For PBC, several studies reported on the change in GLOBE score with second-line therapy. In their open-label prospective trial, Gomez et al ( 7 ) found that the mean GLOBE score decreased from 0.31 to 0.14 among the 78 patients who completed 1 year of OCA. According to the GLOBE score estimates, this translated into an improvement of the projected 10-year risk of LT or death from 20.8% to 17.9% (risk reduction of approximately 14%).…”

“…Nowadays, the GLOBE score is frequently used to assess the potential impact of new drugs in development for PBC. Add-on treatment with obeticholic acid (OCA) or fibrates resulted in a treatment-induced decline of the GLOBE score, based on which clinical benefit was suggested ( 7 – 11 ). However, the change in GLOBE score (delta GLOBE: ΔGLOBE) has never been assessed in relation to the LT-free survival among patients with PBC who were treated with UDCA.…”

The treatment of primary biliary cholangitis: from shadow to light

“…Seventy-eight patients completed the 1-year treatment, of whom 30% achieved a therapeutic response. 72 In an Italian study, 31% of patients had liver cirrhosis. Forty-three percent of patients achieved a therapeutic response.…”

Primary biliary cholangitis: molecular pathogenesis perspectives and therapeutic potential of natural products

“…FXR agonists have been found to be a promising direction for PBC-targeted drug research. The approved FXR agonist OCA has shown outstanding therapeutic efficacy in the clinical treatment of PBC ( 143 ). It is noteworthy that multi-acid receptor agonists have more tremendous therapeutic potential for PBC ( 144 ).…”