|Title||Predictors and Management of Loss of Response to Vedolizumab in Inflammatory Bowel Disease.|
|Publication Type||Journal Article|
|Year of Publication||2018|
|Authors||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, 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|
|Journal||Inflamm Bowel Dis|
|Date Published||2018 10 12|
|Keywords||Adult, 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 Journal||Inflamm Bowel Dis|
|PubMed Central ID||PMC6693035|
|Grant List||KL2 TR001444 / TR / NCATS NIH HHS / United States |
T32 DK007202 / DK / NIDDK NIH HHS / United States