Plant D, et al. - Candidates were estimated to examine the gene expression biomarkers of the methotrexate (MTX) response by analyzing whole blood samples from subjects with rheumatoid arthritis (RA) at 2-time points ie, pretreatment and 4 weeks after initiation of MTX. They developed a highly predictive classifier of MTX nonresponse using L2-regularized logistic regression based on the ratio of transcript values ie, the difference in log₂-transformed expression values between 4 weeks of treatment and pretreatment. They observed vital overrepresentation of type I interferon signaling pathway genes in nonresponders at pretreatment and at 4 weeks after treatment initiation in the pathway analysis of gene networks.