S0652 Real World Exposure-Response Relationship of Vedolizumab in Inflammatory Bowel Disease: A Pooled Multicenter Observational Cohort Analysis of Clinical and Modeled Pharmacological Data

INTRODUCTION: The role of vedolizumab (VDZ) therapeutic drug monitoring in patients with ulcerative colitis (UC) or Crohn's disease (CD) is under investigation. However, a thorough understanding of the relationship between VDZ serum concentrations and clinical outcomes is lacking. METHODS: ERELATE was a retrospective cohort study conducted at 9 centers in 6 countries. Data were pooled from real-world clinical cohorts of patients with UC or CD treated with VDZ. Clinically important treatment outcomes based on definitions commonly used across centers were collected at Weeks 14, 26, and 52. Using a population pharmacokinetic model,1 VDZ dosing, baseline body weight, and albumin concentration were used to predict VDZ concentrations. A Bayesian approach incorporated observed VDZ concentrations to refine individual predicted concentrations. Relationships between predicted concentrations and observed clinically important outcomes were investigated. VDZ concentration thresholds were determined using the optimal Youden index point along the receiver operating characteristic curve. Correlation and agreement between observed and predicted concentrations were evaluated using Spearman (ρ) and intra-class correlation (ICC) coefficients, respectively. RESULTS: In total 695 patients (304 UC, 391 CD) were included; 47.9% were male. Median age was 39 years, median disease duration was 9 years, and 86.3% had prior anti-tumor necrosis factor exposure. Clinically important outcome rates for UC and CD are shown in Table 1. Significant correlation ([ρ = 0.879; P < 0.01] across all timepoints) and agreement (ICC = 0.722; P < 0.01) were noted between observed and predicted concentrations, indicating adequate Bayesian model prediction of individual VDZ concentrations. Observed exposure-response relationships were more pronounced in UC than CD. Differences in VDZ concentration and drug concentration area under the curve from Weeks 0–6 were observed between remitters and non-remitters for UC and CD combined (Table 2). Predicted VDZ concentrations of 30.8 and 33.8 µg/mL at Week 6 and 16.6 and 14.4 µg/mL at Week 14 were associated with clinical remission and deep remission, respectively, at Week 52. CONCLUSION: These real-world data confirm GEMINI trial findings of significant relationships between VDZ serum concentration and clinical outcomes. Adequate drug concentrations during induction therapy may be important predictors of short- and long-term treatment outcomes.Table 1.: Clinically Important Outcomes in Patients With UC or CDTable 2.: Predicted Vedolizumab Trough Concentrations Associated With Clinical and Deep Remission in Patients With UC or CD

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