Soluble Mucosal Addressin Cell Adhesion Molecule 1 and Retinoic Acid are Potential Tools for Therapeutic Drug Monitoring in Patients with Inflammatory Bowel Disease Treated with Vedolizumab: A Proof of Concept Study

Soluble Mucosal Addressin Cell Adhesion Molecule 1 and Retinoic Acid are Potential Tools for... Abstract Background Vedolizumab (VDZ), a humanized monoclonal antibody targeting α4β7 integrin, is effective in induction and maintenance therapy in patients with inflammatory bowel disease (IBD) who have not adequately responded to standard therapies, and high levels of vedolizumab trough levels (VTL) have been associated with clinical remission. The α4β7 integrin binds to endothelial MAdCAM-1 and is up-regulated by retinoic acid (RA). Aim To determine the relations between soluble MAdCAM-1 (sMAdCAM-1) and RA concentrations with clinical remission during VDZ maintenance therapy. Methods In a retrospective study performed in IBD patients treated with VDZ we measured VTL, sMAdCAM-1 and RA concentrations. Results Among the 62 included patients (38 Crohn’s disease) 24 relapsed and 38 stayed in remission between weeks 10 to 30 after VDZ initiation. During this maintenance therapy, median values of VTL and RA were 15.4 µg/mL and 0.97 ng/mL, whereas sMAdCAM-1 was undetectable (< 0.41 ng/mL) in 67.3% of samples. The positive predictive value (PPV) of undetectable sMAdCAM-1 for clinical remission was 80.0% with a corresponding sensitivity of 74.6%. On multivariate analysis undetectable sMAdCAM-1 and high VTL (> 19 µg/mL) were independently associated with clinical remission (OR=7.5, p=0.006 and OR=2.2, p=0.045, respectively). The combination of sMAdCAM-1 < 0.41 ng/mL and VTL > 19 µg/mL was the best pharmacokinetic profile with a PPV of 95.2%. Median values of sMAdCAM-1 and RA were significantly higher (p=0.0001) before VDZ therapy than during the follow-up (sMAdCAM-1: 40.5 vs < 0.41 ng/mL; RA: 1.7 vs 0.97 ng/mL). Only RA > 1.86 ng/mL before VDZ therapy was predictive of clinical remission during the follow-up (AUROC=80.7%). Conclusions Undetectable sMAdCAM-1 appears strongly associated with clinical remission during VDZ maintenance therapy. Combination of undetectable sMAdCAM-1 with high VTL is also potentially interesting for therapeutic drug monitoring. Baseline RA concentrations are predictive of clinical remission. These findings need to be confirmed in further prospective studies. soluble MAdCAM-1, retinoic acid, vedolizumab, inflammatory bowel disease, therapeutic drug monitoring Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Crohn's and Colitis Oxford University Press

Soluble Mucosal Addressin Cell Adhesion Molecule 1 and Retinoic Acid are Potential Tools for Therapeutic Drug Monitoring in Patients with Inflammatory Bowel Disease Treated with Vedolizumab: A Proof of Concept Study

Loading next page...
 
/lp/ou_press/soluble-mucosal-addressin-cell-adhesion-molecule-1-and-retinoic-acid-Qnxe9CNF78
Publisher
Elsevier Science
Copyright
Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com
ISSN
1873-9946
eISSN
1876-4479
D.O.I.
10.1093/ecco-jcc/jjy077
Publisher site
See Article on Publisher Site

Abstract

Abstract Background Vedolizumab (VDZ), a humanized monoclonal antibody targeting α4β7 integrin, is effective in induction and maintenance therapy in patients with inflammatory bowel disease (IBD) who have not adequately responded to standard therapies, and high levels of vedolizumab trough levels (VTL) have been associated with clinical remission. The α4β7 integrin binds to endothelial MAdCAM-1 and is up-regulated by retinoic acid (RA). Aim To determine the relations between soluble MAdCAM-1 (sMAdCAM-1) and RA concentrations with clinical remission during VDZ maintenance therapy. Methods In a retrospective study performed in IBD patients treated with VDZ we measured VTL, sMAdCAM-1 and RA concentrations. Results Among the 62 included patients (38 Crohn’s disease) 24 relapsed and 38 stayed in remission between weeks 10 to 30 after VDZ initiation. During this maintenance therapy, median values of VTL and RA were 15.4 µg/mL and 0.97 ng/mL, whereas sMAdCAM-1 was undetectable (< 0.41 ng/mL) in 67.3% of samples. The positive predictive value (PPV) of undetectable sMAdCAM-1 for clinical remission was 80.0% with a corresponding sensitivity of 74.6%. On multivariate analysis undetectable sMAdCAM-1 and high VTL (> 19 µg/mL) were independently associated with clinical remission (OR=7.5, p=0.006 and OR=2.2, p=0.045, respectively). The combination of sMAdCAM-1 < 0.41 ng/mL and VTL > 19 µg/mL was the best pharmacokinetic profile with a PPV of 95.2%. Median values of sMAdCAM-1 and RA were significantly higher (p=0.0001) before VDZ therapy than during the follow-up (sMAdCAM-1: 40.5 vs < 0.41 ng/mL; RA: 1.7 vs 0.97 ng/mL). Only RA > 1.86 ng/mL before VDZ therapy was predictive of clinical remission during the follow-up (AUROC=80.7%). Conclusions Undetectable sMAdCAM-1 appears strongly associated with clinical remission during VDZ maintenance therapy. Combination of undetectable sMAdCAM-1 with high VTL is also potentially interesting for therapeutic drug monitoring. Baseline RA concentrations are predictive of clinical remission. These findings need to be confirmed in further prospective studies. soluble MAdCAM-1, retinoic acid, vedolizumab, inflammatory bowel disease, therapeutic drug monitoring Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

Journal of Crohn's and ColitisOxford University Press

Published: May 31, 2018

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off