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1.
  • Kowalec, Kaarina, et al. (author)
  • Common variation near IRF6 is associated with IFN-beta-induced liver injury in multiple sclerosis
  • 2018
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:8, s. 1081-
  • 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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2.
  • Scalfari, Antonio, et al. (author)
  • Smouldering-Associated Worsening in Multiple Sclerosis: An International Consensus Statement on Definition, Biology, Clinical Implications, and Future Directions
  • 2024
  • In: ANNALS OF NEUROLOGY. - 0364-5134 .- 1531-8249.
  • Research review (peer-reviewed)abstract
    • Despite therapeutic suppression of relapses, multiple sclerosis (MS) patients often experience subtle deterioration, which extends beyond the definition of "progression independent of relapsing activity." We propose the concept of smouldering-associated-worsening (SAW), encompassing physical and cognitive symptoms, resulting from smouldering pathological processes, which remain unmet therapeutic targets. We provide a consensus-based framework of possible pathological substrates and manifestations of smouldering MS, and we discuss clinical, radiological, and serum/cerebrospinal fluid biomarkers for potentially monitoring SAW. Finally, we share considerations for optimizing disease surveillance and implications for clinical trials to promote the integration of smouldering MS into routine practice and future research efforts.
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