Maxime Verhoeven
65 Validation of a prediction model for insufficient response to MTX Table 1 Descriptives of the derivation (tREACH) and external validation (U-Act-Early) cohorts. tREACH Derivation cohort N=277 U-Act-Early Validation cohort N=91 P-value Clinical parameters DAS28>3.2 at 3 months 43% 64% 0.006** DAS28>3.2 at 6 months 38% 44% 0.417 Gender, male 30% 36% 0.300 Age, mean ± SD 54 ± 14 53 ± 13 0.498 Baseline DAS28, mean ± SD 5.0 ± 1.1 5.0 ± 1.1 0.613 HAQ >0.6 76% 70% 0.330 Laboratory parameters Erythrocyte folate, median (IQR) # 862 (665 – 1163) 1020 (795 – 1221) 0.006** ABCB1 GG/GA 73% 58% 0.016* ABCC3 TC/CC 66% 67% 0.909 Rheumatoid factor positive 65% 81% 0.007** ACPA positive 71% 79% 0.214 Life style parameters BMI, median (IQR) 25 (23 – 29) 25 (23 – 29) 0.950 Current smokers, n (%) 84 (33) 28 (31) 0.820 Co-medication Other DMARDs 56% 0% <0.001*** Oral glucocorticoids 58% 0% <0.001*** Parenteral glucocorticoids 28% 0% <0.001*** Subcutaneous 0% 0% 1.000 Missing values tREACH: DAS28 at 3 months, n=13; DAS28 at 6 months, n=28; erythrocyte folate, n=78; rheumatoid factor, n=35; BMI, n=3; smoking status, n=21; HAQ, n=18; ABCB1, n=21; ABCC3, n=20. Missing values U-Act-Early: DAS28 at 6 months, n=2; rheumatoid factor, n=1; ACPA status, n=1. Percentages shown are of valid data points. *P<0.05 was considered significant, **P<0.01, ***P<0.001. # expressed in nmol/L Validation of prediction model at 3 months The model combining all predictors accomplished an AUC of 0.75 (95%CI: 0.64-0.85), Figure 1, in U-Act-Early (validation), which means that 75% of the patients could be classified correctly. The strongest predictor for insufficient response to MTX in U-Act- Early was baseline DAS28 >5.1 (p=0.008), Table 2. Odds ratios (ORs) for the predictors DAS28, HAQ, erythrocyte folate, BMI and smoking in U-Act-Early (validation) were in the same direction as in the tREACH (derivation), Table 2. The OR of the ABCC3 SNP was however in the opposite direction in U-Act-Early (OR=0.6, 95%CI: 0.23 – 1.79) compared to tREACH (OR=3.1, 95%CI: 1.39 – 6.94). 4
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