Author information

1 Icahn School of Medicine at Mount Sinai, New York, NY, USA.

2 University of Minnesota, Minneapolis, MN, USA.

3 Cleveland Clinic Foundation, Cleveland, OH, USA.

4 Indiana University, Indianapolis, IN, USA.

5 University of California, San Diego, La Jolla, CA, USA.

6 Mayo Clinic, Rochester, MN, USA.

7 Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.

8 Takeda Pharmaceuticals USA Inc., Deerfield, IL, USA.

9 New York University (NYU), New York, NY, USA.

10 Montefiore Medical Center, New York, NY, USA.

11 North Shore University Hospital, Manhasset, NY, USA.

12 Lenox Hill Hospital, New York, NY, USA.

13 University of Mississippi, Jackson, MS, USA.

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 boweldisease (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.