Prediction of response to interferon therapy in multiple sclerosis

被引：20

作者：

Sellebjerg, F. ^{[1
]}

Sondergaard, H. B. ^{[1
]}

Koch-Henriksen, N. ^{[2
,3
]}

Sorensen, P. S. ^{[1
]}

Oturai, A. B. ^{[1
]}

机构：

[1] Rigshosp, Copenhagen Univ Hosp, Dept Neurol, Danish Multiple Sclerosis Ctr, DK-2100 Copenhagen, Denmark

[2] Univ Copenhagen & Clin Inst, Rigshosp, Danish MS Registry, Danish MS Ctr, Copenhagen, Denmark

[3] Aarhus Univ, Dept Clin Epidemiol, Aarhus, Denmark

来源：

ACTA NEUROLOGICA SCANDINAVICA | 2014年 / 130卷 / 04期

基金：

英国医学研究理事会;

关键词：

pharmacogenetics; interferon-beta; multiple sclerosis; treatment response; BETA THERAPY; BREAKTHROUGH DISEASE; GENE VARIANTS; RISK; IRF5;

D O I：

10.1111/ane.12269

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

ObjectiveSingle 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)-. 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-. MethodsThe 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-. Results62% of patients experienced relapses during the first 2years of treatment, and 32% had disability progression during the first 5years 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 2years of treatment had an increased risk of progression during the first 5years 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. ConclusionsPretreatment relapse rate and clinical disease activity during the first 2years of treatment may be associated with disease progression in MS patients treated with IFN-. Genetic analysis of the studied gene variants do not provide additional information.

引用

页码：268 / 275

页数：8

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