Dataset Information

Vitamin D Is Associated with α4β7+ Immunophenotypes and Predicts Vedolizumab Therapy Failure in Patients with Inflammatory Bowel Disease.

ABSTRACT:

Background and aims

Vitamin D downregulates the in vitro expression of the gut-tropic integrin α4β7 on immune cells. The clinical relevance of this finding in patients with inflammatory bowel disease [IBD] is unclear. We tested the hypothesis that vitamin D is associated with α4β7 immunophenotypes and risk of vedolizumab [anti-α4β7] failure in IBD.

Methods

We performed single-cell immunophenotyping of peripheral and intestinal immune cells using mass cytometry [CyTOF] in vedolizumab-naïve patients with IBD [N = 48]. We analysed whole-genome mucosal gene expression [GSE73661] from GEMINI I and GEMINI long-term safety [LTS] to determine the association between vitamin D receptor [VDR] and integrin alpha-4 [ITGA4] and beta-7 [ITGB7] genes. We estimated the odds of vedolizumab failure with low pre-treatment vitamin D in a combined retrospective and prospective IBD cohort [N = 252] with logistic regression.

Results

Immunophenotyping revealed that higher 25[OH]D was associated with decreased α4β7+ peripheral blood mononuclear cells [R = -0.400, p <0.01] and α4β7+ intestinal leukocytes [R = -0.538, p = 0.03]. Serum 25[OH]D was inversely associated with α4β7+ peripheral B cells and natural killer [NK] cells and α4β7+ intestinal B cells, NK cells, monocytes, and macrophages. Mucosal expression of VDR was inversely associated with ITGA4 and ITGB7 expression. In multivariate analysis, 25[OH]D <25 ng/mL was associated with increased vedolizumab primary non-response during induction (odds ratio [OR] 26.10, 95% confidence interval [CI] 14.30-48.90, p <0.001) and failure at 1-year follow-up [OR 6.10, 95% CI 3.06-12.17, p <0.001].

Conclusions

Low serum 25[OH]D is associated with α4β7+ immunophenotypes and predicts future vedolizumab failure in patients with IBD.

Podcast

This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

SUBMITTER: Gubatan J

PROVIDER: S-EPMC8684474 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

Vitamin D Is Associated with α4β7+ Immunophenotypes and Predicts Vedolizumab Therapy Failure in Patients with Inflammatory Bowel Disease.

Gubatan John J Rubin Samuel J S SJS Bai Lawrence L Haileselassie Yeneneh Y Levitte Steven S Balabanis Tatiana T Patel Akshar A Sharma Arpita A Sinha Sidhartha R SR Habtezion Aida A

Journal of Crohn's & colitis 20211201 12

<h4>Background and aims</h4>Vitamin D downregulates the in vitro expression of the gut-tropic integrin α4β7 on immune cells. The clinical relevance of this finding in patients with inflammatory bowel disease [IBD] is unclear. We tested the hypothesis that vitamin D is associated with α4β7 immunophenotypes and risk of vedolizumab [anti-α4β7] failure in IBD.<h4>Methods</h4>We performed single-cell immunophenotyping of peripheral and intestinal immune cells using mass cytometry [CyTOF] in vedolizum ...[more]

PMID: 34180967

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Project description:BackgroundVedolizumab (VDZ) is a well-established and important therapeutic option in the treatment of patients with inflammatory bowel disease (IBD). However, the significance of therapeutic drug monitoring (TDM) with VDZ remains a contradictory field in daily clinical practice. Our study aims to clarify the predictive impact of VDZ drug levels in long-term clinical outcomes in a real-world cohort.MethodsPatients with moderate to severe ulcerative colitis (UC) and Crohn's disease (CD) from a tertiary IBD referral center at the University Hospital Augsburg, Germany, were enrolled in this single-center retrospective data analysis. Clinical and endoscopic data were collected at month 6, month 12, and at the last time of follow-up, and outcomes were correlated with VDZ levels at week 6.ResultsThis study included 95 patients, 68.4% (n = 65) with UC, 24.2% (n = 23) with CD, and 7.4% (n = 7) with indeterminate colitis (CI). Patients with a mean VDZ treatment time of 17.83 months ± 14.56 showed clinical response in 29.5% (n = 28) and clinical remission in 45.3% (n = 43) at the end of the study. Endoscopic response occurred in 20.0% (n = 19) and endoscopic remission in 29.5% (n = 28) at the end of the study. The sustained beneficial effect of VDZ was also reflected in a significant change in biomarker levels. VDZ trough level at week 6 was determined in 48.4% (n = 46) with a mean of 41.79 µg/mL ± 24.58. A significant association between VDZ level at week 6 and both short and long-term outcomes could not be demonstrated. However, numerically higher VDZ levels were seen in patients with endoscopic and clinical improvement at month 6 and at the time of last follow-up.ConclusionsThis study demonstrated efficacy and safety for VDZ in a real-world cohort. Although, for some parameters, a clear trend for higher VDZ levels at week 6 was seen, the efficacy of VDZ was not significantly correlated to VDZ level at week 6, which questions the predictive value of VDZ levels in the real world.

Dataset Information

Vitamin D Is Associated with α4β7+ Immunophenotypes and Predicts Vedolizumab Therapy Failure in Patients with Inflammatory Bowel Disease.

Background and aims

Methods

Results

Conclusions

Podcast

Publications

Vitamin D Is Associated with α4β7+ Immunophenotypes and Predicts Vedolizumab Therapy Failure in Patients with Inflammatory Bowel Disease.

Similar Datasets

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