Figure 2

A) Replication of mRNA as stratification biomarkers for anti-TNF-response in 59 patients from cohort B. Each dot shows one gene, and the Y-axis shows association strength. For each of 7 published studies, all reported genes were investigated for association to anti-TNF-response. Four different models were calculated: three linear regressions with different covariate setups, and one binary-response/no-response setup set at ΔDAS28-CRP < −1.2. The strongest covariates reported in the respective studies are indicated by the color code in the legend. B) Comparison with mRNA expression data from Toonen et al. (GSE33377). The X- and Y-axis shows the log10(P)-value for association with TNFi response for each measured gene, from the Combine and the GSE33377 data, respectively. The compared P-values were calculated based on binary response/no-response. C) Replication of serum protein expression biomarkers sICAM1 and CXCL13 previously reported by Dennis et al. (14). Protein levels were divided by median values for each of the two proteins as indicated along X-axis. The P-value was calculated for a linear regression over the four levels. Each dot shows one patient. Color coding and symbol shape indicate baseline DAS28-CRP and gender. D) ROC plot illustrating the ability to estimate if a patient will have more or less than -1.2 ΔDAS28-CRP values, based on the fitted values of a model containing the 11 predictive biomarkers. This curve shows how different threshold levels will affect the rate of true and false positives predicted: the interpretation of the area under curve (AUC) is that 81.5% of randomly selected TNFi responders will have a higher test result than randomly selected non-responders.