Prediction of response to interferon therapy in multiple sclerosis

Research output: Contribution to journalJournal articleResearchpeer-review

F Sellebjerg, Helle Bach Søndergaard, N Koch-Henriksen, P S Sørensen, A B Oturai

OBJECTIVE: Single nucleotide polymorphisms (SNPs) in the genes encoding interferon response factor (IRF)-5, IRF-8 and glypican-5 (GPC5) have been associated with disease activity in multiple sclerosis (MS) patients treated with interferon (IFN)-β. We analysed whether SNPs in the IRF5, IRF8 and GPC5 genes are associated with clinical disease activity in MS patients beginning de novo treatment with IFN-β.

METHODS: The SNPs rs2004640, rs3807306 and rs4728142 in IRF5, rs13333054 and rs17445836 in IRF8 and rs10492503 in GPC5 were genotyped in 575 patients with relapsing-remitting MS followed prospectively after the initiation of their first treatment with IFN-β.

RESULTS: 62% of patients experienced relapses during the first 2 years of treatment, and 32% had disability progression during the first 5 years of treatment. Patients with a pretreatment annualized relapse rate >1 had an increased risk of relapse (hazard ratio 1.53, 95% confidence interval 1.24-1.90) and progression (hazard ratio 1.48, 95% confidence interval 1.10-1.99) on treatment and patients with breakthrough relapses in the form of relapses during the first 2 years of treatment had an increased risk of progression during the first 5 years of treatment (hazard ratio 2.04, 95% confidence interval 1.47-2.85).The gene variants in IRF5, IRF8 and GPC5 were not associated with risk of relapse or disease progression.

CONCLUSIONS: Pretreatment relapse rate and clinical disease activity during the first 2 years of treatment may be associated with disease progression in MS patients treated with IFN-β. Genetic analysis of the studied gene variants do not provide additional information.

Original languageEnglish
JournalActa Neurologica Scandinavica
Volume130
Issue number4
Pages (from-to)268-275
Number of pages8
ISSN0001-6314
DOIs
Publication statusPublished - 2014

    Research areas

  • Adult, Disease Progression, Female, Genetic Predisposition to Disease, Glypicans, Humans, Interferon Regulatory Factors, Interferon-beta, Male, Middle Aged, Multiple Sclerosis, Relapsing-Remitting, Polymorphism, Single Nucleotide, Recurrence

ID: 138180008