330 Type I, III, and IV collagen degradation fragments are decreased in patients with stricturing (Montreal B2) CD and accurately differentiate them from both non-stricturing, nonpenetrating (Montreal B1) and penetrating (Montreal B3) CD Subsequently, the ability of serum biomarkers to differentiate between Montreal disease behavior subclasses was determined using ROC statistics and logistic regression modeling (Table 3, Figures 3-4, Tables S3-4). Unadjusted analyses revealed that serum C1M, C3M, and C4M levels accurately discriminated between patients with non-stricturing, non-penetrating disease and stricturing disease (AUC with 95% CI: C1M 0.69[0.56-0.83], P<0.01; C3M 0.66[0.53-0.80], P<0.05; C4M 0.68[0.55-0.82], P<0.05) (Figures 3A-C, Table S3). Using multivariable (backwards) logistic regression analyses, allowing adjustment for confounders (history of ileocaecal resection, concurrent use of immunosuppressive drugs, and platelet counts), all biomarkers retained their ability to differentiate between non-stricturing, non-penetrating and stricturing CD (Figures 3EG, I-K). In these analyses, CRP dropped out as a non-significant confounding factor, but to doublecheck whether these results remained robust while adjusting for CRP, analyses were repeated accordingly, which demonstrated comparable results (Table S5).When combining the biomarkers with their residual values (derived from linear regression, corrected for significant confounders), the discriminative ability of C3M was superior in differentiating between non-stricturing, nonpenetrating and stricturing CD (AUC 0.91[0.83-0.98], P<0.001), followed by serum C4M levels (AUC 0.87[0.79-0.96], P<0.001) and C1M levels (AUC 0.78[0.67-0.98], P<0.001) (Table S4). Figure 3 | Capacity of serological biomarkers of type I, III, and IV collagen degradation (C1M, C3M and C4M, respectively) and the type IV collagen formation/degradation ratio (PRO-C4/C4M ratio) to discriminate between non-stricturing, non-penetrating (Montreal B1) and stricturing (Montreal B2) CD. Unadjusted (A-D) and adjusted (E-H) ROC curves demonstrate significant discriminative capacity of serum C1M, C3M, and C4M levels and the PRO-C4/C4M ratiowith regard to non-stricturing, non-penetrating disease (B1) vs. stricturing disease (B2). Predicted probabilities (I-L) derived from the multivariable logistic regression models, representing the odds of having stricturing (Montreal B2) CD and determining the course of the ROC curves as shown in panels E-H, are substantially separated between both disease behavior subtypes. The lines with associated 95% confidence intervals (color shade) represent the fitted logistic regression lines. Abbreviations: AUC, area under the ROC curve. Chapter 10
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