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

Shmidt E1,2, Kochhar G3, Hartke J4, Chilukuri P4, Meserve J5, Chaudrey K6, Koliani-Pace JL7, Hirten R1, Faleck D1, Barocas M8, Luo M8, Lasch K8, Boland BS5, Singh S5, Casteele NV5, Sagi SV4, Fischer M4, Chang S9, Bohm M4, Lukin D10, Sultan K11, Swaminath A12, Hudesman D9, Gupta N13, Kane S6, Loftus EV Jr6, Sandborn WJ5, Siegel CA7, Sands BE1, Colombel JF1, Shen B3, Dulai PS5. Inflamm Bowel Dis. 2018 May 18. doi: 10.1093/ibd/izy171. [Epub ahead of print]

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.


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.

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