Maxime Verhoeven

75 Validation of a prediction model for insufficient response to MTX SUPPLEMENTARY FILE Supplementary Figure S1 ROC curve for the prediction of non-response (DAS28>3.2) to MTX after 6 months of treatment. Area under the curve (AUC) is reported as follows: AUC (95% confidence interval). Predictors were: baseline DAS28 >5.1, baseline HAQ >0.6, ABCB1 genotype, ABCC3 genotype, baseline erythrocyte folate, BMI >25kg/ m 2 and current smoking. Supplementary Table S1 Effect sizes of multivariable logistic regression models for insufficient response to MTX (DAS28>3.2) at 3 months of treatment in the combined data set. U-Act-Early + tREACH Combination cohorts N=264 Predictors OR (95%CI) DAS28 >5.1 3.6 (1.98 – 6.47)** HAQ >0.6 2.1 (1.08 – 3.90)* ABCB1 GG/GA 1.2 (0.71 – 2.17) ABCC3 TC/CC 1.8 (0.99 – 3.11) Folate <750 nmol/L 1.9 (1.06 – 3.50)* Smoker 2.2 (1.23 – 4.00)** BMI >25 kg/m 2 1.9 (1.11 – 3.31)* AUC (95%CI) 0.74 (0.68 – 0.80) Model shown is from the combined data set (U-Act-Early + tREACH). OR= odds ratio, CI= confidence interval. Predictors that contributed significantly to the model were indicated with an asterisk, where *P<0.05 and **P<0.01. 4

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