276 Table 3 | ROC analysis showing discriminative power of individual inflammatory biomarkers that are significantly increased in IBD patients with moderate (2) or severe (3) endoscopic disease activity as compared to patients with remission (0) or mild (1) disease activity, as determined by the binary categorized, composite IBD endoscopy score (CD: SES-CD, UC: Mayo endoscopic subscore). *P-values were calculated for the difference between the area under the ROC curve and the no-discrimination line (AuROC = 0.50). *P-values < 0.05 were considered statistically significant. **P < 0.01. ***P < 0.001. Best combinations of inflammatory biomarkers to predict endoscopic disease activity To achieve the best discrimination between remission (0) or mild (1) vs. moderate (2) or severe (3) endoscopic disease activity, multiple combinations of detected inflammatory biomarkers were empirically investigated for their predictive accuracy. Ultimately, for the composite IBD endoscopy score, the best predictive combination of inflammatory biomarkers was represented by the assembly of serum levels of SAA, IL-6, IL-8 and Eotaxin-1, showing an AuROC of 0.84 (SE: 0.05, 95% CI: 0.73 – 0.94, P < 0.0001, n = 64) (Figure 4A). In this combination, SAA could be replaced by serum CRP levels without losing predictive accuracy (correlation between CRP and SAA: ρ = 0.663, P < 0.01) (Supplementary Figure S6). Applying the algorithm for comparison of correlated ROC curves, the AuROC for this combination of biomarkers was significantly better as compared to that of serum CRP levels (P = 0.002), whereas no statistical significance emerged when compared to fecal calprotectin levels or the clinical disease scores (HBI/SCCAI) (P = 0.313 and P = 0.073, respectively). Fecal calprotectin levels closest to the date of endoscopy were incorporated into the analysis (n = 25, all within 3 months, median [IQR] time interval 39 [25;55] days). Serum CRP levels had an AuROC of 0.57 (SE: 0.07, 95% CI: 0.43 – 0.72, P = 0.32), fecal calprotectin (FC) levels 0.66 (n = 25, SE: 0.12, 95% CI: 0.44 – 0.90, P = 0.17) and HBI or SCCAI scores 0.66 (n = 56, SE: 0.09, 95% CI: 0.49 – 0.83, P = 0.08) (Figure 4B-D). The resulting combined calculated probability had a maximum sensitivity of 90.7% and specificity of 68.4% in correctly discriminating IBD patients with low or high endoscopic disease activity (Youden’s J-statistic = 0.58). Chapter 8 Table 3. ROC analysis showing discriminative power of individual inflammatory biomarkers that are significantly increased in IBD pat moderate (2) or severe (3) endoscopic disease activity as compared to pati ts with remis ion (0) or mild (1) disease ac the binary categorized, composite IBD endoscopy score (CD: SES-CD, UC: Mayo endoscopic subscore). AuROC (95% CI) Sensitivity / Specificity Cut-off value Youden’s J statistic Inflammatory biomarkers Eotaxin-1 (ng/ml) 0.75 (0.62 – 0.87) 74.5% / 66.7% > 0.21 ng/ml 0.41*** SAA (mg/l) 0.75 (0.62 – 0.87) 48.8% / 95.2% > 17.5 mg/l 0.44** TNF-α (pg/ml) 0.65 (0.52 – 0.78) 38.3% / 87.5% > 2.88 pg/ml 0.26* IL-6 (pg/ml) 0.67 (0.53 – 0.81) 55.3% / 72.7% > 0.91 pg/ml 0.28* IL-8 (pg/ml) 0.70 (0.58 – 0.83) 68.1% / 66.7% > 6.12 pg/ml 0.35** IL-17A (pg/ml) 0.72 (0.57 – 0.86) 66.7% / 68.2% > 2.40 pg/ml 0.35** Routine measures CRP (mg/l) 0.57 (0.43 – 0.72) 51.1% / 66.7% > 5.73 mg/l 0.18 FC (µg/g) 0.66 (0.44 – 0.90) 80.1% / 50.0% > 735 µg/g 0.32 HBI/SCCAI 0.66 (0.49 – 0.83) 62.9% / 64.3% > 6.5 points 0.27 *P-values were calculated for the difference between the area under the ROC curve and the no-discrimination line (AuROC = 0.50). *P-values < 0.05 were considered statistically significant. **P < 0.01. ***P < 0.001.
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