Young Investigator: Vedolizumab Trough Levels in Inflammatory Bowel Disease: Initial Clinical Experience

BACKGROUND: Therapeutic drug monitoring is an integral part of inflammatory bowel disease (IBD) management. Vedolizumab trough level evaluation has recently become available, but the clinical utility and optimal cutoff value of these levels have not been well defined. The aims of this study are to determine: 1) the median vedolizumab trough level and frequency of detectable antibodies; 2) the effect of concomitant corticosteroids and combination immunomodulator therapy on vedolizumab trough level; 3) the correlation of vedolizumab tough levels with C-reactive protein (CRP) and mucosal healing (MH); and 4) change in clinical management based on vedolizumab trough levels. METHODS: A retrospective study of IBD patients treated with vedolizumab from January 1st 2008 to March 1st 2017 at our institution was conducted. Patients who have had vedolizumab trough levels checked were included in the study. Data were abstracted for demographics, smoking status, and IBD disease and management details. Endoscopic and CRP data were collected if they were performed within 3 months and 30 days of vedolizumab trough level, respectively. Outcomes included: median vedolizumab level in the cohort; presence of anti-vedolizumab antibodies; effect of corticosteroids and concomitant immunomodulator therapy on vedolizumab levels; and median vedolizumab level associated with normal CRP (< 3 mg/dL) and MH. RESULTS: A total of 50 patients (68% CD, 26% UC, 6% indeterminate colitis) were included in the study. The median age was 43 (range, 16-86) years and 42% were male. Combination therapy with immunomodulators was employed in 18 patients (13 with thiopurines; 5 with methotrexate). Concomitant corticosteroid use was noted in 28%. Vedolizumab was administered every 8 weeks (n=36), 6 weeks (n=5) and 4 weeks (n=9). The median vedolizumab trough level was 14.75 (0-49.6) ug/mL. None of the patients had any detectable anti-vedolizumab antibodies. The median vedolizumab trough level was 13.8 (3.5-43) ug/mL and 14.8 (0-49.6) ug/mL in patients on and off corticosteroids, respectively (P=0.65). In patients on combination therapy with immunomodulators, the median vedolizumab trough level was 10.2 (0-49.5) ug/mL vs. 15.1 (3-49.6) ug/mL in patients on monotherapy (P=0.56). Endoscopic assessment and CRP levels were performed in 28 patients. MH was achieved in 18% (n=5). The median vedolizumab trough level was 11.2 (5.9-19.2) ug/mL and 9.1 (0-19.6) ug/mL in patients with and without MH, respectively (P=0.86). Patients with a normal CRP had a median vedolizumab trough level of 11.4 (3.5-38.7) ug/mL compared to 14.7 (0-49.6) ug/mL in those with high CRP (P=0.67). Vedolizumab trough levels resulted in change in clinical management in 80% of the cohort which included: decrease in dose interval in 33 patients, discontinuation of vedolizumab in 6 patients, and addition of an immunomodulator in 3 patients. CONCLUSION(S): In a clinical cohort of IBD patients treated with vedolizumab, the median tough level was approximately 15 ug/mL, and no anti-drug antibodies were detected. Concomitant corticosteroid and immunomodulator therapy did not affect vedolizumab trough levels. No correlation between vedolizumab trough level with MH and CRP could be found. However, our results are limited by the small sample size.