Vedolizumab Therapeutic Drug Monitoring and Real-World Outcomes in Inflammatory Bowel Disease

United European Gastroenterology Journal

Date:

October 2, 2021

Authors:

W. Afif, J.K. Marshall, E.L. Stewart, O. Kaidanovich-Beilin, C. Pettengell, R. Ward, C.H. Seow

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Introduction

The present study evaluates the relationships between post-induction vedolizumab trough concentrations (VTC) and real-world outcomes in inflammatory bowel disease (IBD), including biomarkers of inflammation and clinical disease scores.

Aims & Methods

Participants in the Takeda Canada Patient Support Program who were treated with vedolizumab for Crohn’s disease (CD) and ulcerative colitis (UC) were assessed at defined timepoints from 2018-2020. Post-induction VTC (Week 14), baseline albumin (Week 0), faecal calprotectin (FC; Week 0 and 30), C-reactive protein (CRP; Week 0 and 30), Harvey-Bradshaw Index (HBI; Week 0 and 30) and Partial Mayo Scores (PMS; Week 0 and 30) were collected. Remission was defined by CRP (<5mg/L), FC (<250µg/g), HBI (<5), or PMS (<3) at Week 30. Receiver operating characteristic (ROC) curve analyses were used to measure the sensitivity, specificity, and optimal cut-point value of VTC for multiple definitions of remission. In multivariate analyses, covariates included optimal VTC threshold, age, sex, disease subtype, baseline albumin, disease duration, and biologic treatment exposure.

Results

IBD patients who achieved CRP remission at Week 30 had higher Week 14 VTC levels than those who did not (n=210, p=0.0001). Among all patients, a Week 14 VTC cut-off of 17.35µg/mL (n=210, Area Under the ROC (AUROC): 0.67, 95% Confidence Interval (CI): 0.59-0.74, p<0.001) best predicted CRP remission by multivariate analysis (p=0.001). VTC cut-offs best predicting CRP remission were similar between subgroups (CD VTC>19.60µg/mL, p=0.01 (AUROC: 0.69, 95% CI: 0.60-0.78, p<0.001); UC VTC>17.35µg/mL, p=0.005 (AUROC: 0.64, 95% CI: 0.52-0.76, p<0.001)). Patients with Week 14 VTC levels above the determined cut-off remained on vedolizumab treatment for longer than those below this cut-off (n=210; VTC>17.35µg/mL Hazard Ratio: 0.44, 95% CI: 0.20-0.99, log-rank p=0.04). Week 14 VTC levels were higher in IBD patients who achieved FC remission compared with those who did not (n=144, p=0.02). A Week 14 cut-off of 18.55µg/mL (n=144, AUROC: 0.61, 95% CI: 0.52-0.70, p<0.001) was associated with FC remission by univariate (p=0.005) analysis, but not in multivariate analysis. In all patients, baseline albumin levels were independently associated with FC remission by multivariate analysis (n=144, p=0.03). In CD patients, FC remission was associated with baseline albumin levels (n=79, p=0.04) and female sex (n=79, p=0.02), both by multivariate analysis. There were no associations found between Week 14 VTC and Week 30 disease activity index scores in UC or CD patients by multivariate analysis.

Conclusion

Monitoring VTC in early treatment of CD and UC may predict patient outcomes as measured by CRP. Baseline normal albumin in all patients and female sex in CD patients are associated with improved FC remission, likely related to decreased clearance of vedolizumab.