Prediction of response to interferon therapy in multiple sclerosis

Objective Single nucleotide polymorphisms ( SNP s) in the genes encoding interferon response factor ( IRF )‐5, IRF ‐8 and glypican‐5 ( GPC 5) have been associated with disease activity in multiple sclerosis ( MS ) patients treated with interferon ( IFN )‐ β . We analysed whether SNP s in the IRF 5 , IRF 8 and GPC 5 genes are associated with clinical disease activity in MS patients beginning de novo treatment with IFN ‐ β . Methods The SNP s rs2004640, rs3807306 and rs4728142 in IRF 5 , rs13333054 and rs17445836 in IRF 8 and rs10492503 in GPC 5 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 IRF 5 , IRF 8 and GPC 5 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.