P518 Vedolizumab trough concentrations are associated with endoscopic response in patients with inflammatory bowel disease

Abstract

Background: Vedolizumab (VDZ) is an effective therapy for Crohn's disease (CD) and ulcerative colitis (UC). Therapeutic drug monitoring may guide the use of VDZ to improve outcomes. We aim to investigate the association between VDZ trough level (TL) and clinical, biochemical and endoscopic outcomes. Method(s): We recruited patients on VDZ for treatment for CD or UC from February 2016 to June 2017; including a prospective cohort which was assessed at Weeks 6, 10, 14, 30, and 54 and a cross-sectional cohort that was assessed at one or more of these time points. Clinical (defined as clinical remission with Harvey Bradshaw Index [HBI] score <5/Partial Mayo score [PMS] < 2), biochemical (C-reactive protein [CRP] normalisation with serum CRP <5mg/l and faecal calprotectin [FCP] normalisation with level <250 mug/g) and endoscopic (endoscopic remission with Simple Endoscopic score for CD [SESCD] score of <2/Mayo endoscopy score [MES] of <2; endoscopic response with 50% reduction of SESCD/>=1 MES reduction) endpoints were correlated with VDZ TL and antibody levels (A-VDL). VDZ TL and A-VDL testing were performed with an ELISA based assay (LISA TRACKERR, Theradiag France). Result(s): Combined assessment for 40 patients (median age 49, 57.5% male, 55% CD, 22.5% on immunomodulator and 15% biologic naive) with outcome data at Week 30 or beyond showed 62.5% clinical remission rate, 48.7% CRP normalisation, 48.5% FCP normalisation, 46.9% (N = 15 of 32) endoscopic response and 21.9% endoscopic remission. Endoscopic response rates were numerically higher in UC than in CD patients (62.5% vs. 31.3%, p = 0.156) and 31.3% of the endoscopic cohort patients were on every four-week dosing. In the combined CD and UC cohort, VDZ TL >=15 mug/ml showed a trend toward association with endoscopic response (59.1% vs. 20%, p = 0.079). Significant association was found in the CD subset (N = 16) where TL >=22 mug/ml was associated with endoscopic response (62.5% vs. 0%, p = 0.026). Mean TL was significantly higher in CD patients with endoscopic response than in UC (mean 38.8 +/- 11.1 vs. 20.8 +/- 10.4, p = 0.014). Week 14 (N = 11, CD and UC) TL of >12.1 mug/ml also showed association with endoscopic response (100% vs. 16.7%, p = 0.015) at Week 30 or beyond. No definitive relationship between VDZ TL and clinical or biochemical outcomes were demonstrated. No anti-VDZ antibodies were identified. Conclusion(s): Vedolizumab serum trough level is associated with endoscopic response, particularly in Crohn's disease where higher concentrations may be required to achieve endoscopic improvement than in ulcerative colitis.