Dataset Information

Fecal calprotectin is an early predictor of endoscopic response and histologic remission after the start of vedolizumab in inflammatory bowel disease.

ABSTRACT:

Background and aims

Early prediction of the effect of vedolizumab (VDZ) in inflammatory bowel disease (IBD) is of paramount importance to guide clinical decisions. This study assessed whether early fecal calprotectin (FC) can predict endoscopic response and histologic remission after VDZ initiation.

Methods

This was a prospective study. Inclusion criteria were endoscopic inflammation and FC?>100?µg/g. FC was determined at baseline and weeks 2, 4, 8 and 16. At week 16, endoscopies with ileal and colonic biopsies were performed. FC changes were assessed with Wilcoxon Rank Sum tests. ROC statistics were used to assess the diagnostic accuracy of FC.

Results

In total, 45 patients [27 Crohn's disease (CD), 16/2 ulcerative colitis (UC)/IBD-unclassified] [40% males, median age 39 (28-51) years] were included. Week 16 endoscopic response and histologic remission rates were 58% and 33%. A median 37% decline in FC at week 2 was observed only in endoscopic responders, p?=?0.025. FC?<250?µg/g at week 8 predicted endoscopic response in both UC and CD (positive predictive value 100%), whereas absence of FC decline at week 8 corresponded with absence of endoscopic response in CD [negative predictive value (NPV) 82%] and absence of histologic remission in both UC and CD (NPV 90%).

Conclusion

The onset of a decline in FC as early as week 2 is associated with endoscopic response to VDZ induction. FC?<250?µg/g at week 8 is associated with endoscopic response, whereas absence of FC decline at week 8 is associated with absence of both endoscopic response and histologic remission. FC levels 8?weeks after the start of VDZ could be used to guide clinical decisions and might substitute for endoscopic response evaluation.

SUBMITTER: Pauwels RWM

PROVIDER: S-EPMC7768861 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Fecal calprotectin is an early predictor of endoscopic response and histologic remission after the start of vedolizumab in inflammatory bowel disease.

Pauwels Renske W M RWM van der Woude Christien J CJ Erler Nicole S NS de Vries Annemarie C AC

Therapeutic advances in gastroenterology 20201224

<h4>Background and aims</h4>Early prediction of the effect of vedolizumab (VDZ) in inflammatory bowel disease (IBD) is of paramount importance to guide clinical decisions. This study assessed whether early fecal calprotectin (FC) can predict endoscopic response and histologic remission after VDZ initiation.<h4>Methods</h4>This was a prospective study. Inclusion criteria were endoscopic inflammation and FC >100 µg/g. FC was determined at baseline and weeks 2, 4, 8 and 16. At week 16, endoscopies ...[more]

PMID: 33488771

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Project description:Background and aimThe association of fecal calprotectin (FC) and endoscopic response in inflammatory bowel disease patients during vedolizumab (VDZ) treatment is largely unknown. The aim of this study is to assess the diagnostic value of FC to predict endoscopic response.MethodsPatients with active endoscopic disease at baseline were included. Endoscopies and FC tests were performed at baseline and week 16. Patients with a confirmed endoscopic response at week 16 continued VDZ maintenance therapy, and endoscopy and FC tests were performed at week 52. Endoscopic response was defined as endoscopic Mayo score reduction of ≥ 1, SES-CD of ≥ 50%, or Rutgeerts' score of ≥ 1. Correlations were assessed using Spearman and receiver operating characteristic statistics.ResultsA total of 114 patients, 46 ulcerative colitis and 68 Crohn's disease patients (44 men, median age 40 years), were included after the start of VDZ; 85% was anti-tumor necrosis factor alpha refractory. Endoscopic response was observed in 60 (53%) patients at week 16; the response sustained in 73% at week 52. FC decreased significantly from 819 at baseline to 154 μg/g at week 16. FC at weeks 16 and 52 were significantly correlated to (sustained) endoscopic response (r = -0.62 / r = -0.67, P < 0.001). FC < 200 μg/g indicates endoscopic response (area under the curve = 0.89, positive predictive value = 94%), whereas FC > 450 μg/g indicates endoscopic non-response after induction (negative predictive value = 83%). An increase in FC level of > 400 μg/g after induction indicates endoscopic loss of response (area under the curve = 0.97, negative predictive value = 96%).ConclusionThis prospective study demonstrates a significant correlation between FC and endoscopic response to VDZ. FC < 200 μg/g prognosticate endoscopic response, and FC > 450 μg/g endoscopic non-response. An increase in FC of > 400 μg/g after induction indicates endoscopic loss of response. This simple FC algorithm may guide clinical decisions on the continuation and optimization of VDZ in inflammatory bowel disease patients.

Project description:BACKGROUND & AIMS:We aimed to identify biomarkers that might be used to predict responses of patients with inflammatory bowel diseases (IBD) to vedolizumab therapy. METHODS:We obtained biopsies from inflamed colon of patients with IBD who began treatment with vedolizumab (n = 31) or tumor necrosis factor (TNF) antagonists (n = 20) and performed RNA-sequencing analyses. We compared gene expression patterns between patients who did and did not enter endoscopic remission (absence of ulcerations at month 6 for patients with Crohn's disease or Mayo endoscopic subscore ?1 at week 14 for patients with ulcerative colitis) and performed pathway analysis and cell deconvolution for training (n = 20) and validation (n = 11) datasets. Colon biopsies were also analyzed by immunohistochemistry. We validated a baseline gene expression pattern associated with endoscopic remission after vedolizumab therapy using 3 independent datasets (n = 66). RESULTS:We identified significant differences in expression levels of 44 genes between patients who entered remission after vedolizumab and those who did not; we found significant increases in leukocyte migration in colon tissues from patients who did not enter remission (P < .006). Deconvolution methods identified a significant enrichment of monocytes (P = .005), M1-macrophages (P = .05), and CD4+ T cells (P = .008) in colon tissues from patients who did not enter remission, whereas colon tissues from patients in remission had higher numbers of naïve B cells before treatment (P = .05). Baseline expression levels of PIWIL1, MAATS1, RGS13, and DCHS2 identified patients who did vs did not enter remission with 80% accuracy in the training set and 100% accuracy in validation dataset 1. We validated these findings in the 3 independent datasets by microarray, RNA sequencing and quantitative PCR analysis (P = .003). Expression levels of these 4 genes did not associate with response to anti-TNF agents. We confirmed the presence of proteins encoded by mRNAs using immunohistochemistry. CONCLUSIONS:We identified 4 genes whose baseline expression levels in colon tissues of patients with IBD associate with endoscopic remission after vedolizumab, but not anti-TNF, treatment. We validated this signature in 4 independent datasets and also at the protein level. Studies of these genes might provide insights into the mechanisms of action of vedolizumab.

Dataset Information

Fecal calprotectin is an early predictor of endoscopic response and histologic remission after the start of vedolizumab in inflammatory bowel disease.

Background and aims

Methods

Results

Conclusion

Publications

Fecal calprotectin is an early predictor of endoscopic response and histologic remission after the start of vedolizumab in inflammatory bowel disease.

Similar Datasets

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