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 Vincent Loftus, Jr, William J. Sandborn, Corey A. Siegel, Bruce E. Sands, Jean Frederic Colombel, Bo Shen, Parambir S. Dulai

Research output: Contribution to journalArticle

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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 - Oct 12 2018

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Inflammatory Bowel Diseases
Crohn Disease
C-Reactive Protein
vedolizumab
Tumor Necrosis Factor-alpha
Confidence Intervals
Kaplan-Meier Estimate
Ulcerative Colitis
Registries

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

Cite this

Shmidt, E., Kochhar, G., Hartke, J., Chilukuri, P., Meserve, J., Chaudrey, K., ... 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

Predictors and Management of Loss of Response to Vedolizumab in Inflammatory Bowel Disease. / Shmidt, Eugenia; Kochhar, Gursimran; Hartke, Justin; Chilukuri, Prianka; Meserve, Joseph; Chaudrey, Khadija; Koliani-Pace, Jenna L.; Hirten, Robert; Faleck, David; Barocas, Morris; Luo, Michelle; Lasch, Karen; Boland, Brigid S.; Singh, Siddharth; Vande Casteele, Niels; Sagi, Sashidhar Varma; Fischer, Monika; Chang, Shannon; Bohm, Matthew; Lukin, Dana; Sultan, Keith; Swaminath, Arun; Hudesman, David; Gupta, Nitin; Kane, Sunanda; Loftus, Jr, Edward Vincent; Sandborn, William J.; Siegel, Corey A.; Sands, Bruce E.; Colombel, Jean Frederic; Shen, Bo; Dulai, Parambir S.

In: Inflammatory Bowel Diseases, Vol. 24, No. 11, 12.10.2018, p. 2461-2467.

Research output: Contribution to journalArticle

Shmidt, E, Kochhar, G, Hartke, J, Chilukuri, P, Meserve, J, Chaudrey, K, Koliani-Pace, JL, Hirten, R, Faleck, D, Barocas, M, Luo, M, Lasch, K, Boland, BS, Singh, S, Vande Casteele, N, Sagi, SV, Fischer, M, Chang, S, Bohm, M, Lukin, D, Sultan, K, Swaminath, A, Hudesman, D, Gupta, N, Kane, S, Loftus, Jr, EV, Sandborn, WJ, Siegel, CA, Sands, BE, Colombel, JF, Shen, B & Dulai, PS 2018, 'Predictors and Management of Loss of Response to Vedolizumab in Inflammatory Bowel Disease', Inflammatory Bowel Diseases, vol. 24, no. 11, pp. 2461-2467. https://doi.org/10.1093/ibd/izy171
Shmidt E, Kochhar G, Hartke J, Chilukuri P, Meserve J, Chaudrey K et al. Predictors and Management of Loss of Response to Vedolizumab in Inflammatory Bowel Disease. Inflammatory Bowel Diseases. 2018 Oct 12;24(11):2461-2467. https://doi.org/10.1093/ibd/izy171
Shmidt, Eugenia ; Kochhar, Gursimran ; Hartke, Justin ; Chilukuri, Prianka ; Meserve, Joseph ; Chaudrey, Khadija ; Koliani-Pace, Jenna L. ; Hirten, Robert ; Faleck, David ; Barocas, Morris ; Luo, Michelle ; Lasch, Karen ; Boland, Brigid S. ; Singh, Siddharth ; Vande Casteele, Niels ; Sagi, Sashidhar Varma ; Fischer, Monika ; Chang, Shannon ; Bohm, Matthew ; Lukin, Dana ; Sultan, Keith ; Swaminath, Arun ; Hudesman, David ; Gupta, Nitin ; Kane, Sunanda ; Loftus, Jr, Edward Vincent ; Sandborn, William J. ; Siegel, Corey A. ; Sands, Bruce E. ; Colombel, Jean Frederic ; Shen, Bo ; Dulai, Parambir S. / Predictors and Management of Loss of Response to Vedolizumab in Inflammatory Bowel Disease. In: Inflammatory Bowel Diseases. 2018 ; Vol. 24, No. 11. pp. 2461-2467.
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title = "Predictors and Management of Loss of Response to Vedolizumab in Inflammatory Bowel Disease",
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.",
author = "Eugenia Shmidt and Gursimran Kochhar and Justin Hartke and Prianka Chilukuri and Joseph Meserve and Khadija Chaudrey and Koliani-Pace, {Jenna L.} and Robert Hirten and David Faleck and Morris Barocas and Michelle Luo and Karen Lasch and Boland, {Brigid S.} and Siddharth Singh and {Vande Casteele}, Niels and Sagi, {Sashidhar Varma} and Monika Fischer and Shannon Chang and Matthew Bohm and Dana Lukin and Keith Sultan and Arun Swaminath and David Hudesman and Nitin Gupta and Sunanda Kane and {Loftus, Jr}, {Edward Vincent} and Sandborn, {William J.} and Siegel, {Corey A.} and Sands, {Bruce E.} and Colombel, {Jean Frederic} and Bo Shen and Dulai, {Parambir S.}",
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TY - JOUR

T1 - Predictors and Management of Loss of Response to Vedolizumab in Inflammatory Bowel Disease

AU - Shmidt, Eugenia

AU - Kochhar, Gursimran

AU - Hartke, Justin

AU - Chilukuri, Prianka

AU - Meserve, Joseph

AU - Chaudrey, Khadija

AU - Koliani-Pace, Jenna L.

AU - Hirten, Robert

AU - Faleck, David

AU - Barocas, Morris

AU - Luo, Michelle

AU - Lasch, Karen

AU - Boland, Brigid S.

AU - Singh, Siddharth

AU - Vande Casteele, Niels

AU - Sagi, Sashidhar Varma

AU - Fischer, Monika

AU - Chang, Shannon

AU - Bohm, Matthew

AU - Lukin, Dana

AU - Sultan, Keith

AU - Swaminath, Arun

AU - Hudesman, David

AU - Gupta, Nitin

AU - Kane, Sunanda

AU - Loftus, Jr, Edward Vincent

AU - Sandborn, William J.

AU - Siegel, Corey A.

AU - Sands, Bruce E.

AU - Colombel, Jean Frederic

AU - Shen, Bo

AU - Dulai, Parambir S.

PY - 2018/10/12

Y1 - 2018/10/12

N2 - 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.

AB - 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.

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DO - 10.1093/ibd/izy171

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