Abstract
Introduction: The disease severity index (DSI) for inflammatory bowel disease (IBD) is a novel tool that encapsulates the burden of illness but requires endoscopic assessment. The neutrophil biomarkers faecal calprotectin (fCal) and myeloperoxidase (fMPO) are significantly associated with endoscopic IBD activity. fCal is also used as a surrogate treatment target for the management of IBD. This study aimed to develop a non-invasive DSI using these biomarkers (DSI-fCal and DSI-fMPO) instead of colonoscopy and investigated whether these indices were associated with a complicated IBD course.
Methods: Adults with IBD were recruited prospectively at the time of disease assessment via colonoscopy and followed for 24 months. Baseline biomarker concentrations were used to recalculate the mucosal inflammation criterion of the DSI in place of colonoscopy ( Figure 1). These thresholds were identified from previous paired colonoscopy-biomarker analyses.2 The DSI-fCal and DSI-fMPO were correlated with IBD symptoms, endoscopic activity, and quality-of-life (QoL). Area under the receiver-operating-characteristics curves (AUROC) was used to identify optimal DSI thresholds predicting a complicated IBD course at 24 months (need for escalation of biological/immunomodulator or recurrent corticosteroids for disease relapse, IBD-hospitalisations, and/or surgeries). Multivariable logistic regression (adjusting for baseline symptoms and endoscopic disease activity) assessed the utility of the DSI-fCal and DSI-fMPO in predicting this primary study endpoint.
Results: In total, 171 patients were included (99 Crohn’s disease (CD), 90 female, median age=46y (IQR 36-59), median disease duration=13y (IQR 5-22)). A complicated IBD course was observed in 71 patients at 24 months. DSI-fCal was significantly correlated with endoscopic indices (CD, r=0.49, <0.001; ulcerative colitis (UC), r=0.65, p<0.001), symptoms (CD, r=0.53, <0.001; UC, r=0.71, p<0.001) and QoL (r=-0.58, p<0.001). DSI-fMPO was also correlated with endoscopic indices (CD, r=0.45, p<0.001; UC, r=0.63, p<0.001), symp-toms (CD, r=0.58, <0.001; UC, r=0.74, p<0.001) and QoL (r=-0.57, p<0.001). DSI-fCal (AUROC=0.83, <0.001; Optimal threshold-28. Sensitivity 76%, Specificity 82%) and DSI- fMPO (AUROC=0.80, p<0.001; Optimal threshold=25, Sensitivity=76%, Specificity 82%) were non-inferior in predicting a complicated IBD course as the original DSI (Pdiference>0.05) (Figure 2). The non-invasive DSI was independently associated with a complicated IBD course on multivariable analyses (DSI-fCal2s, aOR-6.04, 95% CI 2.42-15.08; DSI-fMPO25, aOR=7.84, 95% CI 2.96-20.73).
Conclusions: Non-invasive forms of the DSI (DSI-fCal and DSI-fMPO) were significantly associated with endoscopic, symptom and QoL indices in IBD. These novel indices performed similarly in prognosticating the longitudinal disease course as the original index.