Characteristics associated with drug-induced liver injury from interferon beta in multiple sclerosis patients

Expert Opin Drug Saf. 2014 Oct;13(10):1305-17. doi: 10.1517/14740338.2014.947958. Epub 2014 Aug 18.


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.

Keywords: IFN-β; adverse drug reactions; drug-induced liver injury; multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • British Columbia / epidemiology
  • Canada / epidemiology
  • Chemical and Drug Induced Liver Injury / epidemiology
  • Chemical and Drug Induced Liver Injury / etiology*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunologic Factors / adverse effects*
  • Immunologic Factors / therapeutic use
  • Interferon-beta / adverse effects*
  • Interferon-beta / therapeutic use
  • Male
  • Middle Aged
  • Multiple Sclerosis / drug therapy
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Sex Factors
  • Sweden / epidemiology
  • Time Factors
  • United States / epidemiology


  • Immunologic Factors
  • Interferon-beta