title: Combined ursodeoxycholic acid (UDCA) and fenofibrate in primary biliary cholangitis patients with incomplete UDCA response may improve outcomes.
abstract: BACKGROUND
  Fibrates appear to improve biochemistry in patients with primary biliary cholangitis (PBC), but it is unclear which factors predict response and whether treatment improves transplant-free survival.
  
  
  OBJECTIVE
  To evaluate biochemical profiles, liver-related outcomes and adverse events following fenofibrate therapy in PBC patients with incomplete response to ursodeoxycholic acid (UDCA).
  
  
  METHODS
  A retrospective cohort study was performed at a tertiary centre. Cox regression was used to compare outcomes between patients treated with fibrates and UDCA (FF) or UDCA alone, adjusted for a propensity score to account for treatment selection bias.
  
  
  RESULTS
  A total of 120 patients were included (FF group n = 46, UDCA group n = 74, median fenofibrate treatment 11 months); 41% vs. 7% met the Toronto criteria for biochemical response [alkaline phosphatase ≤1.67 times the upper limit of normal] in the FF and UDCA groups, respectively (P = 0.0001). Fenofibrate was also associated with improved decompensation-free and transplant-free survival [hazard ratio (HR) 0.09, 95% CI 0.03-0.32, P = 0.0002]. However, only fenofibrate use, not biochemical response, was independently associated with improved outcomes on multivariable analysis (HR 0.40, 95% CI 0.17-0.93, P = 0.03). Twenty-two percent discontinued fenofibrate due to adverse events (most common: abdominal pain and myalgias). In cirrhotic patients, bilirubin increased more rapidly in the FF group (P = 0.005).
  
  
  CONCLUSIONS
  Fenofibrate therapy is associated with significant improvement in alkaline phosphatase, decompensation-free and transplant-free survival in PBC patients with incomplete UDCA response. However, fenofibrate should be used cautiously in cirrhosis, with close monitoring for clinical/biochemical decompensation. Additional studies are required to assess the validity of alkaline phosphatase as an appropriate response criteria for fibrate therapy.
authors.affiliation: Toronto Centre for Liver Disease, Toronto Western and General Hospital, University Health Network, University of Toronto, Toronto, Canada.
authors.forename: A C
authors.initials: AC
authors.lastname: Cheung
authors.affiliation: Mount Sinai Hospital and Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Lapointe-Shaw
authors.affiliation: Toronto Centre for Liver Disease, Toronto Western and General Hospital, University Health Network, University of Toronto, Toronto, Canada.|Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Kowgier
authors.affiliation: Department of Gastroenterology and Hepatology, Hospital Español, Mexico D.F, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: Meza-Cardona
authors.affiliation: Centre for Liver Research, National Institute for Health Research Biomedical Research Unit, University of Birmingham, Birmingham, UK.
authors.forename: G M
authors.initials: GM
authors.lastname: Hirschfield
authors.affiliation: Toronto Centre for Liver Disease, Toronto Western and General Hospital, University Health Network, University of Toronto, Toronto, Canada.
authors.forename: H L A
authors.initials: HL
authors.lastname: Janssen
authors.affiliation: Toronto Centre for Liver Disease, Toronto Western and General Hospital, University Health Network, University of Toronto, Toronto, Canada.|McLaughlin-Rotman Centre for Global Health, University of Toronto, Toronto, Canada.
authors.forename: J J
authors.initials: JJ
authors.lastname: Feld
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism; D002756:Cholagogues and Choleretics / Q000008:administration & dosage / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage*; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid; D000469:Alkaline Phosphatase; D001663:Bilirubin; D011345:Fenofibrate