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.
Acknowledgments
We are grateful to Naga Chalasani, MD, for facilitating access to the DILIN case data and for helpful comments on the manuscript and to Pär Hallberg, PhD, for access to the clinical data related to the SWEDEGENE samples. We thank Tom Duggan, Yinshan Zhao, PhD and Feng Zhu (Division of Neurology, University of British Columbia) for help with data handling and coding. We thank all multiple sclerosis clinic patients for sharing their clinical information. We also thank the BCMS Clinic neurologists who contributed to the study through patient examination and data collection (current members listed here): A. Traboulsee, MD, FRCPC (UBC Hospital MS Clinic Director and Head of the UBC MS Programs); A-L Sayao, MD, FRCPC; V Devonshire, MD, FRCPC; S Hashimoto, MD, FRCPC; J Hooge, MD, FRCPC; L Kastrukoff, MD, FRCPC; J Oger, MD, FRCPC; D Adams, MD, FRCPC; D Craig, MD, FRCPC; S Meckling, MD, FRCPC; L Daly, MD, FRCPC; O Hrebicek, MD, FRCPC; D Parton, MD, FRCPC and K Pope, MD, FRCPC. KK was funded by the Canadian Institutes of Health Research (Doctoral award) and the University of British Columbia. HT is funded by the Multiple Sclerosis Society of Canada (Don Paty Career Development Award); is a Michael Smith Foundation for Health Research Scholar and the Canada Research Chair for Neuroepidemiology and Multiple Sclerosis. EK was funded by the Michael Smith Foundation for Health Research (Postdoctoral Fellowship). RAM was funded in part by a Don Paty Career Development Award from the MS Society of Canada. MW was funded by Swedish Research Council (Medicine 523-2008-5568). BC was funded by the Canadian Institutes of Health Research, Genome Canada and the Child & Family Research Institute (Vancouver, Canada).