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- Kowalec, Kaarina, et al.
(author)
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Characteristics associated with drug-induced liver injury from interferon beta in multiple sclerosis patients
- 2014
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In: Expert Opinion on Drug Safety. - : Informa Healthcare. - 1474-0338 .- 1744-764X. ; 13:10, s. 1305-1317
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Research review (peer-reviewed)abstract
- Objective: To identify and characterize drug-induced liver injury (DILI) associated with IFN-beta in multiple sclerosis (MS) using recommended criteria. Methods: This retrospective, mixed methods design included a cohort of IFN-beta 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-beta 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-beta exposed MS patients met criteria for DILI, with a trend toward an increased risk for women and those exposed to IFN-beta-1a SC (44 mcg 3 x 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-beta exposed patients developed DILI in BC, Canada. Identification of DILI cases from diverse sources highlighted that this reaction occurs even after years of exposure.
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| 2. |
- Kowalec, Kaarina, et al.
(author)
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Common variation near IRF6 is associated with IFN-beta-induced liver injury in multiple sclerosis
- 2018
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:8, s. 1081-
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Journal article (peer-reviewed)abstract
- Multiple sclerosis (MS) is a disease of the central nervous system treated with disease-modifying therapies, including the biologic, interferon-β (IFN-β). Up to 60% of IFN-β-exposed MS patients develop abnormal biochemical liver test results1,2, and 1 in 50 experiences drug-induced liver injury3. Since genomic variation contributes to other forms of drug-induced liver injury4,5, we aimed to identify biomarkers of IFN-β-induced liver injury using a two-stage genome-wide association study. The rs2205986 variant, previously linked to differential expression of IRF6, surpassed genome-wide significance in the combined two-stage analysis (P = 2.3 × 10–8, odds ratio = 8.3, 95% confidence interval = 3.6–19.2). Analysis of an independent cohort of IFN-β-treated MS patients identified via electronic medical records showed that rs2205986 was also associated with increased peak levels of aspartate aminotransferase (P = 7.6 × 10–5) and alkaline phosphatase (P = 4.9 × 10-4). We show that these findings may be applicable to predicting IFN-β-induced liver injury, offering insight into its safer use.
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| 3. |
- McKay, Kyla A, et al.
(author)
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Risk of Multiple Sclerosis in People Living with HIV: An International Cohort Study.
- 2023
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In: Annals of neurology. - 1531-8249. ; 95:3, s. 487-94
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Journal article (peer-reviewed)abstract
- There has been interest in a possible negative association between HIV and multiple sclerosis (MS). We aimed to compare the risk of MS in a cohort of individuals living with HIV to that in the general population.Population-based health data were accessed for 2 cohorts of HIV-positive persons from Sweden and British Columbia, Canada. Incident MS was identified using MS registries or a validated algorithm applied to administrative data. Individuals with HIV were followed from 1year after the first clinical evidence of HIV or the first date of complete administrative health data (Canada= April 1, 1992 and Sweden=January 1, 2001) until the earliest of incident MS, emigration, death, or study end (Canada=March 31, 2020 and Sweden=December 31, 2018). The observed MS incidence rate in the HIV-positive cohort was compared to the expected age-, sex-, calendar year-, income-specific, and region of birth-specific rates in a randomly selected sample of >20% of each general population. The standardized incidence ratio (SIR) for MS following the first antiretroviral therapy exposure ("ART-exposed") was also calculated.The combined Sweden-Canada cohort included 29,163 (75% men) HIV-positive persons. During 242,248 person-years of follow-up, 14 incident MS cases were observed in the HIV-positive cohort, whereas 26.19 cases were expected. The SIR for MS in the HIV-positive population was 0.53 (95% confidence interval [CI]=0.32-0.90). The SIR for MS following the first ART exposure was 0.55 (95% CI=0.31-0.96).This international population-based study demonstrated a lower risk of MS among HIV-positive individuals, and HIV-positive ART-exposed individuals. These findings provide support for further exploration into the relationship among HIV, ART, and MS. ANN NEUROL 2023.
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