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

TitlePredictors and Management of Loss of Response to Vedolizumab in Inflammatory Bowel Disease.
Publication TypeJournal Article
Year of Publication2018
AuthorsShmidt 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, Casteele NVande, Sagi SVarma, Fischer M, Chang S, Bohm M, Lukin D, Sultan K, Swaminath A, Hudesman D, Gupta N, Kane S, Loftus EV, Sandborn WJ, Siegel CA, Sands BE, Colombel J-F, Shen B, Dulai PS
JournalInflamm Bowel Dis
Date Published2018 10 12
KeywordsAdult, Antibodies, Monoclonal, Humanized, Biomarkers, C-Reactive Protein, Colitis, Ulcerative, Crohn Disease, Disease Management, Female, Follow-Up Studies, Gastrointestinal Agents, Humans, Male, Middle Aged, Prognosis, Prospective Studies, Retrospective Studies, Risk Assessment, ROC Curve, Severity of Illness Index

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.

Alternate JournalInflamm Bowel Dis
PubMed ID29788240
PubMed Central IDPMC6693035
Grant ListKL2 TR001444 / TR / NCATS NIH HHS / United States
T32 DK007202 / DK / NIDDK NIH HHS / United States