Predictors and management of loss of response to vedolizumab in inflammatory bowel disease

Eugenia Shmidt, Gursimran Kochhar, Justin Hartke, Prianka Chilukuri, Joseph Meserve, Khadija Chaudrey, Jenna L. Koliani-Pace, Robert Hirten, David Faleck, Morris Barocas, Michelle Luo, Karen Lasch, Brigid S. Boland, Siddharth Singh, Niels Vande Casteele, Sashidhar Varma Sagi, Monika Fischer, Shannon Chang, Matthew Bohm, Dana LukinKeith Sultan, Arun Swaminath, David Hudesman, Nitin Gupta, Sunanda Kane, Edward V. Loftus, William J. Sandborn, Corey A. Siegel, Bruce E. Sands, Jean Frederic Colombel, Bo Shen, Parambir S. Dulai

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Background: We quantified loss of response (LOR) to vedolizumab (VDZ) in clinical practice and assessed the effectiveness of VDZ dose intensification for managing LOR. Methods: Retrospective review (May 2014-December 2016) of a prospectively maintained inflammatory bowel disease (IBD) registry. Kaplan- Meier estimates were used to determine rates of LOR to VDZ. Independent predictors of LOR were identified using univariate and multivariable Cox proportional hazard regression. Success of recapturing response (> 50% reduction in symptoms from baseline) and remission (complete resolution of symptoms) after dose intensification was quantified. Results: Cumulative rates for VDZ LOR were 20% at 6 months and 35% at 12 months, with slightly lower rates in Crohn's disease than in ulcerative colitis (6 months 15% vs 18% and 12 months 30% vs 39%, P = 0.03). On multivariable analysis, LOR to a tumor necrosis factor (TNF) antagonist before VDZ use was associated with an increased risk for LOR to VDZ [hazard ratio (HR) 1.93; 95% confidence interval (CI) 1.25-2.97] in all patients. For Crohn's disease patients specifically, higher baseline C-reactive protein concentration was associated with increased risk for LOR to VDZ (HR 1.01 per mg/dL increase, 95% CI 1.01-1.02). Shortening of VDZ infusion interval from 8 to every 4 or 6 weeks recaptured response in 49% and remission in 18% of patients. Conclusions: LOR to a TNF antagonist before VDZ use and higher baseline C-reactive protein are important predictors of VDZ LOR. Treatment response can be recaptured in almost half of these patients with VDZ infusion interval shortening.

Original languageEnglish (US)
Pages (from-to)2461-2467
Number of pages7
JournalInflammatory bowel diseases
Volume24
Issue number11
DOIs
StatePublished - Nov 1 2018

Keywords

  • Biologics
  • Crohn's disease
  • Inflammatory bowel disease
  • Ulcerative colitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

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    Shmidt, E., Kochhar, G., Hartke, J., Chilukuri, P., Meserve, J., Chaudrey, K., Koliani-Pace, J. L., Hirten, R., Faleck, D., Barocas, M., Luo, M., Lasch, K., Boland, B. S., Singh, S., Casteele, N. V., Sagi, S. V., Fischer, M., Chang, S., Bohm, M., ... Dulai, P. S. (2018). Predictors and management of loss of response to vedolizumab in inflammatory bowel disease. Inflammatory bowel diseases, 24(11), 2461-2467. https://doi.org/10.1093/IBD/IZY171