Additive beneficial effects of Fibrates combined with Obeticholic acid in the treatment of patients with Primary Biliary Cholangitis and inadequate response to second-line therapy: data from the Italian PBC Study Group

Abstract

Obeticholic acid (OCA) and fibrates are the only therapies, which have shown biochemical benefit in PBC patients with inadequate response to ursodeoxycholic acid (UDCA). However, the efficacy of their combination is unknown. Aim of our study was to investigate the efficacy of a combined therapy with OCA and fibrateson the liver biochemistry in high-risk PBC patients, i.e. those with inadequate response to UDCA. This is a proof-of-concept retrospective cohort study. Patients with PBC treated with at least 12 weeks with combination therapy of UDCA (13-15 mg/kg/day), OCA (5-10 mg/daily) and fibrates (bezafibrate 400 mg/daily or fenofibrate 200 mg/daily) were included. Demographical, clinical and biochemical data were collected and analysed before starting the second line therapy, before starting the third line therapy and after 3-6 months of triple therapy. Eleven PBC patients from three liver centres in Italy were included. Median ALP level at the start of the second line therapy was 273U/L (interquartile range, IQR 203,311) with a median reduction of 22%[-0.9,35]. The median ALP level at the start of the third line therapy was 232U/L[199,293] with a median reduction of 29%[22,48] (Figure 1). Eight patients experienced any reduction in ALP levels during triple therapy.The median bilirubin level at the start of the second line therapy was of 0.72 mg/dL[0.6,1] with a median reduction of 13%[-36,20]. The median bilirubin level at the start of the third line therapy was 0.80 mg/dL[0.7,0.9] with a median reduction of 3%[-5,18]. One patient dropped out for persistently abnormal transaminases secondary to introduction of bezafibrates. Triple therapy with UDCA, OCA and fibrates improves liver biochemistry and increases the rate of ALP normalization in patients with PBC and an inadequate response to OCA/UDCA or fibrates/UDCA dual therapy. A randomized clinical trial to assess the efficacy and safety of triple therapy in high-risk PBC patients is warranted.