Dataset Information

Early vedolizumab trough levels predict combined endoscopic and clinical remission in inflammatory bowel disease.

ABSTRACT:

Background

The relationship between vedolizumab trough levels and combined endoscopic and clinical remission is unknown.

Objective

To compare vedolizumab trough levels in patients with and without combined remission within the first year of treatment.

Methods

We prospectively collected vedolizumab trough levels in 51 consecutive patients (28 Crohn's disease (CD) and 23 ulcerative colitis (UC)) before all infusions up to week 22, and at weeks 38 and 54, with concentrations measured after study completion. Centrally read endoscopy was performed at a median of 46 weeks. The primary outcome was combined endoscopic (CD: Simple endoscopic score for CD (SES-CD) < 4 without ulceration; UC: Mayo endoscopic subscore ≤ 1) and clinical remission (CD: resolution of abdominal pain; UC: resolution of rectal bleeding; both: resolution of altered bowel habit).

Results

Median vedolizumab trough levels at weeks 6 (25.7 vs 15.6 µg/mL; P = 0.015) and 22 (15.1 vs 4.9 µg/mL; P = 0.001) were higher in patients with combined remission. A threshold of 22 µg/mL at week 6 (area under the curve (AUC) 0.733; 95% confidence interval 0.567-0.899) and 8 µg/mL at week 22 (AUC 0.819; 95% confidence interval 0.692-0.946) predicted combined remission.

Conclusion

Early vedolizumab trough levels predicted combined endoscopic and clinical remission highlighting their possible use in clinical practice.

SUBMITTER: Hanzel J

PROVIDER: S-EPMC6620872 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Early vedolizumab trough levels predict combined endoscopic and clinical remission in inflammatory bowel disease.

Hanžel Jurij J Sever Nejc N Ferkolj Ivan I Štabuc Borut B Smrekar Nataša N Kurent Tina T Koželj Matic M Novak Gregor G Compernolle Griet G Tops Sophie S Gils Ann A Drobne David D

United European gastroenterology journal 20190319 6

<h4>Background</h4>The relationship between vedolizumab trough levels and combined endoscopic and clinical remission is unknown.<h4>Objective</h4>To compare vedolizumab trough levels in patients with and without combined remission within the first year of treatment.<h4>Methods</h4>We prospectively collected vedolizumab trough levels in 51 consecutive patients (28 Crohn's disease (CD) and 23 ulcerative colitis (UC)) before all infusions up to week 22, and at weeks 38 and 54, with concentrations m ...[more]

PMID: 31316778

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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

Early vedolizumab trough levels predict combined endoscopic and clinical remission in inflammatory bowel disease.

Background

Objective

Methods

Results

Conclusion

Publications

Early vedolizumab trough levels predict combined endoscopic and clinical remission in inflammatory bowel disease.

Similar Datasets

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