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: firstname.lastname@example.org 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 of Crohn's and Colitis – Oxford University Press
Published: May 31, 2018
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