DEVELOPMENT AND VALIDATION OF A TEST TO MONITOR ENDOSCOPIC ACTIVITY IN PATIENTS WITH CROHN’S DISEASE BASED ON SERUM LEVELS OF PROTEINS.
Gastroenterology. 2019 Nov 08;:
Authors: D’Haens G, Kelly O, Battat R, Silverberg MS, Laharie D, Louis E, Savarino E, Bodini G, Yarur A, Boland BS, Afif W, Li XJ, Hale M, Ho J, Kondragunta V, Huang B, Kuy C, Okada L, Hester KD, Bray KR, Mimms L, Jain A, Singh S, Collins A, Valasek MA, Sandborn WJ, Vermeire S, Dulai PS
BACKGROUND & AIMS: Non-invasive tests to measure endoscopic activity in patients with Crohn’s disease (CD) have limitations. We aimed to develop a test to identify patients in remission, based on endoscopic analysis, and monitor CD activity based on serum levels of proteins.
METHODS: We developed a test to measure 13 proteins in blood (ANG1, ANG2, CRP, SAA1, IL7, EMMPRIN, MMP1, MMP2, MMP3, MMP9, TGFA, CEACAM1, and VCAM1), called the endoscopic healing index [EHI] using samples from 278 patients with CD from multi-national training cohort. We validated the test using 2 independent cohorts of patients with CD: 116 biologic-naïve patients with early-stage CD (validation cohort 1) and 195 biologic-exposed patients with chronic CD (validation cohort 2). The ability of the test to identify patients with active disease vs patients in remission (defined as a simple endoscopic score for CD of ≤ 2 and ≤ 1 in each segment, or a total CD endoscopic index of severity score < 3) was assessed using area under receiver operating characteristic curve (AUROC) analysis. The diagnostic accuracy of the test was compared with that of measurement of serum CRP and fecal calprotectin (FC).
RESULTS: The EHI scores range from 0 to 100 units; higher scores indicate more severe CD activity, based on endoscopy findings. The EHI identified patients in remission with an AUROC of 0.962 in validation cohort 1 (95% CI, 0.942-0.982) and an AUROC of 0.693 in validation cohort 2 (95% CI, 0.619-0.767), regardless of CD location or phenotype. A cut-off value of 20 points identified patients in remission with the highest level of sensitivity (97.1% in validation cohort 1 and 83.2% in validation cohort 2), with specificity values of 69.0% and 36.6%, respectively. A cut-off value of 50 points identified patients in remission with the highest level of specificity (100% in validation cohort 1 and 87.8% in validation cohort 2), with sensitivity values of 37.3% and 30.0%, respectively. The EHI identified patients in remission with a significantly higher AUROC value than the test for CRP (0.876, P<.001 in validation cohort 1 and 0.624, P=.109 in validation cohort 2). In analysis of patients with available FC measurements, the AUROC value for the EHI did not differ significantly from that of measurement of FC (AUROC, 0.950 for EHI vs AUROC, 0.923 for FC, P=.147 in validation cohort 1 and AUROC, 0.803 for EHI vs AUROC, 0.854 for FC, P=.298 in validation cohort 2).
CONCLUSIONS: We developed an index to identify patients with CD in endoscopic remission based on blood levels of 13 proteins, called the EHI. The EHI identified patients with resolution of endoscopic disease activity, with good overall accuracy, although with variation between the 2 cohorts assessed. The EHI AUROC values were comparable to measurement of FC and higher than measurement of serum CRP. The test might be used in practice for assessing endoscopic activity in patients with CD.
PMID: 31711925 [PubMed – as supplied by publisher]