P023 The effective use of bezafibrate as a second line therapy for primary biliary cholangitis

Background Bezafibrate, a peroxisome proliferator-activated receptor alpha agonist, is not often used in the UK for treatment of PBC (primary biliary cholangitis) in patients who don’t respond to ursodeoxycholic acid (UDCA) because it is an unlicensed therapy for this condition. In our liver unit we have used this treatment since 2014. Methods This retrospective case series included all patients who were commenced on bezafibrate from January 2014 to March 2020. 25 patients were listed from our pharmacy database and notes reviewed using a data collection tool. Biochemical and clinical outcomes were recorded over a 12 month period following initiation of bezafibrate in combination with UDCA. 10 patients were excluded due to either: non-compliance; a revised diagnosis of an overlap syndrome or primary sclerosing cholangitis; less than 12 months duration of bezafibrate therapy; lost to follow-up; not fulfilling PBC diagnostic criteria as per The British Society Gastroenterology/UK-PBC management guidelines.1 An inadequate response to UDCA therapy was defined by the ‘Toronto’ biochemical stratification as a serum alkaline phosphatase (ALP) level above 1.67 x upper limit of normal (normal range 30–130 U/L). This value is 217 U/L in our unit. Results The 15 patients were all female with a median age at diagnosis of 49. 67% were positive for anti-mitochondrial antibody or PBC specific anti-nuclear antibody. 33% had consistent liver histology and the median ALP was 477 U/L at diagnosis. The mean duration of UDCA monotherapy was 62 months with a median dose of 19 mg/kg/day (range 11–26). At the time of commencing bezafibrate, the median ALP was 296 U/L (mean 301 U/L), mean ALT was 52 U/L and mean albumin was 36 g/L. The median bilirubin was 8 umol/L (range 5–37) and no patients had evidence of clinically significant portal hypertension. 3 patients had radiological evidence of cirrhosis. The bezafibrate was continued at 400 mg/day in 14 patients and 200 mg/day in 1 patient who developed myalgia. Figure 1 shows the median ALP at the start of bezafibrate therapy and an improvement in median ALP at 6 and 12 months of therapy. After 12 months, the median ALP was 141 U/L with a mean of 178 U/L. 80% of patients (12/15) achieved an ALP of < 217 U/L. Of the 3 who didn’t; 1 died from metastatic breast cancer; 1 was referred for liver transplantation and 1 has commenced obeticholic acid. No patients developed renal impairment. Conclusion Our case series demonstrates that bezafibrate is a highly effective second line therapy for PBC, in combination with UDCA, for patients who don’t have an adequate biochemical response with monotherapy. Reference Hirschfield GM, Dyson JK, Alexander GJM, et al. The british society of gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut 2018;67:1568–1594.

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