title: Characteristics associated with drug-induced liver injury from interferon beta in multiple sclerosis patients.
abstract: OBJECTIVE
  To identify and characterize drug-induced liver injury (DILI) associated with IFN-β in multiple sclerosis (MS) using recommended criteria.
  
  
  METHODS
  This retrospective, mixed methods design included a cohort of IFN-β exposed MS patients from British Columbia (BC), Canada and a series of DILI cases from other Canadian provinces and two adverse drug reaction (ADR) networks (USA and Sweden). Associations between sex, age and IFN-β product, and DILI were explored in BC cohort using Cox proportional hazard analyses. Characteristics, including the time to DILI, were compared between sites.
  
  
  RESULTS
  In BC, 18/942 (1.9%) of IFN-β exposed MS patients met criteria for DILI, with a trend toward an increased risk for women and those exposed to IFN-β-1a SC (44 mcg 3 × weekly) (adjusted Hazard Ratios: 3.15;95% CI:0.72 - 13.72, p = 0.13 and 6.26;95%CI:0.78 - 50.39, p = 0.08, respectively). Twenty-four additional cases were identified from other sites; the median time to DILI was comparable between BC and other Canadian cases (105 and 90 days, respectively), but longer for the ADR network cases (590 days, p = 0.006).
  
  
  CONCLUSIONS
  Approximately 1 in 50 IFN-β exposed patients developed DILI in BC, Canada. Identification of DILI cases from diverse sources highlighted that this reaction occurs even after years of exposure.
authors.affiliation: University of British Columbia (UBC), Neuroscience Program , Room S178, 2211 Wesbrook Mall, Vancouver, British Columbia V6T 2B5 , Canada +1 604 822 0759 ; helen.tremlett@ubc.ca.
authors.forename: Kaarina
authors.initials: K
authors.lastname: Kowalec
authors.forename: Elaine
authors.initials: E
authors.lastname: Kingwell
authors.forename: Eric M
authors.initials: EM
authors.lastname: Yoshida
authors.forename: Ruth Ann
authors.initials: RA
authors.lastname: Marrie
authors.forename: Marcelo
authors.initials: M
authors.lastname: Kremenchutzky
authors.forename: Trudy L
authors.initials: TL
authors.lastname: Campbell
authors.forename: Mia
authors.initials: M
authors.lastname: Wadelius
authors.forename: Bruce
authors.initials: B
authors.lastname: Carleton
authors.forename: Helen
authors.initials: H
authors.lastname: Tremlett
mesh_terms: D000328:Adult; D001955:British Columbia / Q000453:epidemiology; D002170:Canada / Q000453:epidemiology; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects* / Q000627:therapeutic use; D016899:Interferon-beta / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: D007155:Immunologic Factors; D016899:Interferon-beta
keywords: IFN-β; adverse drug reactions; drug-induced liver injury; multiple sclerosis