Differential regulation of interferon (IFN) response genes upon tumor necrosis factor (TNF) blockade and clinical response to treatment. Patients were divided into two groups (ratio < 1 and ratio > 1) on the basis of their IFN response upon TNF blockade and compared with each other with respect to clinical response to treatment. The ratio is determined by the T = 1/T = 0 expression levels of the IFN response genes as demonstrated in Figure 1a. Data are shown as box plots; each box represents the 25th to 75th percentiles. The lines inside represent the median, and the ends of the whiskers represent the smallest and largest observations. Patients with an upregulation in IFN response genes displayed a significantly (unpaired t test, * P < 0.05; **P < 0.01) worse clinical response to treatment as assessed by change in disease activity score (DAS) (DAS before treatment minus DAS 16 weeks after treatment) (a), European League Against Rheumatism (EULAR) response (b), tender joint count (TJC) (c), and Health Assessment Questionnaire-Disability Index (HAQ) (d) after treatment.