LAUSR

Background: Vedolizumab (VDZ) is an anti-integrin biologic used in the treatment of ulcerative colitis (UC) and Crohn's disease (CD). In clinical trials, higher trough levels at weeks 6 and 52 were associated with higher rates of clinical remission. Assays for VDZ levels are becoming commercially available. The aim of this study was to determine the association between trough VDZ levels and remission during maintenance therapy in a real world setting. Methods: We conducted a cross-sectional study of patients undergoing maintenance VDZ therapy at a tertiary care IBD infusion center. UC and CD patients age 6 or older were eligible. All patients had trough serum VDZ and anti-VDZ antibody (ATV) levels measured using a drug tolerant homogeneous mobility shift assay platform (ANSER VDZ, Prometheus Labs Inc., San Diego, CA). Data collected at each infusion visit included patient demographics, C-reactive protein (CRP) levels and disease activity indices including the Harvey Bradshaw Index (HBI) and the Partial Mayo Score (pMS). Descriptive statistics were preformed using means (+/− standard deviation) and proportions. Wilcoxon rank-sum tests, Chi-square tests and univariate logistic regression were used to assess the association between VDZ levels, ATVs and remission, defined as normal CRP (<5 mg/L) and HBI <5 or pMS of 0 or 1. For associations with remission, VDZ levels were reported as the median with interquartile range (IQR). Results: A total of 113 patients were analyzed, 44% CD and 56% UC. Mean age was 33.3 (±15.1) years, 54% were male and 87% were Caucasian. The average disease duration was 12.3 years. 75% of patients had previously been treated with anti-TNF and 41% were concurrently on an immunomodulator. The average number of prior VDZ infusions was 7.9 (±4.4). Overall median VDZ level was 11 &mgr;g/mL (range 1.4–100.1 &mgr;g/mL). Patients in remission had significantly higher median levels of VDZ (12.1 &mgr;g/mL, IQR 9.5–19.9 versus 9.6 &mgr;g/mL, IQR 5.7–16.9, P = 0.01). Findings were similar in UC patients (median 14.3 versus 9.8 &mgr;g/mL, P = 0.04). Higher rates of remission were seen with increasing quartiles of VDZ level (P trend = 0.01). Patients with VDZ levels below the median (11 &mgr;g/mL) were significantly less likely to be in remission compared to those above the median (37.9% versus 61.8%, P = 0.01). Patients with VDZ levels above the median had significantly higher odds of being in remission (OR 2.65, 95% CI, 1.24–5.66). No significant differences in VDZ level or remission rate was seen with immunomodulator use. Only 4 patients (3.5%) had detectable ATVs but all 4 had detectable VDZ levels. Three of these 4 patients were not on an immunomodulator. Conclusions: During maintenance therapy, VDZ levels were significantly higher in patients in remission. The odds of remission were significantly higher in patients with VDZ levels in the top 2 quartiles (VDZ level >11 &mgr;g/mL). ATVs were found in only 3.5% of patients.