Preliminary Exploration Of The Dosage And Duration Of Fenofibrate In The Treatment Of Primary Biliary Cholangitis

Objective:To explore the course,long-term efficacy,and safety of fenofibrate for the treatment of primary biliary cholangitis(PBC)patients with incomplete responses to ursodeoxycholic acid(UDCA)and the feasibility of fenofibrate tapering or discontinuation.Methods:We observed the medical records of PBC patients with incomplete responses to UDCA who were admitted to Peking Union Medical College Hospital’s outpatient clinic of the Department of Rheumatology from March 2015 to August 2022 and received fenofibrate 200mg per day in combination with UDCA.Patients were divided into the discontinuation group,the reduced-dose group and the standard-dose group.The changes in biochemical indexes,immunological indexes,lipid levels and drug safety were monitored during the use of fenofibrate at baseline,3,6,12,18,24,30 and 36 months respectively to explore the optimal dosage and course of fenofibrate in the real world.Results:The course of treatment for PBC patients using standard dose of fenofibrate is 6-60 months,with an average course of 13.05±9.40 months.The normal rate of ALP in patients maintaining standard dose of fenofibrate continued to increase to 85.7%,90.9%,and 100.0%at 12,18,and 24 months of treatment,respectively.9.1%and 18.2%of 11 patients who received half-dose fenofibrate after their ALP levels dropped to normal levels,experienced biochemical recurrence at 3 and 24 months of drug reduction,respectively.Elevated ALP level was observed in 92.3%of patients within 6 months after drug discontinuation.The biochemical recurrence rates were 40.0%and 46.7%at 6 and 12 months of discontinuation,respectively.Biochemical indexes improved after returning to the standard dose or reduced dose of fenofibrate.In terms of adverse reactions,4 patients experienced elevated transaminases>2 times the upper limit of normal(ULN).and the level of transaminase decreased significantly after fenofibrate was suspended.The half dose fenofibrate was well tolerated and there was no serious adverse effect.Conclusions:Fenofibrate is safe,effective and can be used for a long term in the treatment of PBC.Long-term use of fenofibrate in combination with UDCA can continuously improve biochemical and immunological indexes after 24 months of follow-up.After discontinuation of fenofibrate,some patients experienced recurrence,so discontinuation is not recommended.Some patients suffered from hepatic injury,and they tolerated the half-dose fenofibrate.Half-dose fenofibrate showed good efficacy in most of the patients.