P964 Vedolizumab trough concentrations during subcutaneous treatment in patients with inflammatory bowel diseases

Abstract

Abstract Background An exposure-response relationship has been described for intravenous (IV) vedolizumab (VDZ), but little is known about through levels and real life outcomes of subcutaneous (SC) VDZ treatment. We aimed to study the effect of SC VDZ in a prospective real life cohort and assessed what clinical variables are associated with vedolizumab trough concentrations. Methods IBD patients initiating VDZ SC treatment were included in our nationwide, prospective Initiative on Crohn and Colitis (ICC) registry. Adult IBD patients were included if a known trough level during IV and SC therapy was available. Two different assays were used for trough levels measurements : i.e. an enzyme linked immunosorbent assay (ELISA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The primary outcome measure was the mean VDZ trough concentration during maintenance treatment (after at least four SC injections). In addition, associations between VDZ serum trough concentrations and corticosteroid-free clinical remission were assessed. A Receiver Operating Characteristic (ROC) analysis was performed to determine the concentration threshold that was associated with corticosteroid free clinical remission after 4 SC VDZ injections (i.e. defined as a Harvey Bradshaw Index (HBI) score ≤ 4 for CD and a Short Clinical Colitis Activity Index (SCCAI) score ≤ 2 for UC). Results In total, 24 with Crohn’s disease (CD) and 32 with ulcerative colitis (UC) patients were included. Twelve patients started SC VDZ after a maximum of three VDZ infusions and 44 patients switched to VDZ SC after at least four VDZ infusions. The mean VDZ trough concentration was 34.4 µg/mL (SD 12.9) after 13 (IQR 11-20) weeks of SC treatment. The mean VDZ trough concentration increased from 20.5 µg/mL to 35.2 µg/mL (P < 0.001) in patients who switched from IV to SC VDZ. Biochemical remission (defined as a C-reactive protein (CRP) ≤ 5 µg/mL with a faecal calprotectin (FC) ≤ 250 µg/g) prior to the switch, VDZ measurements using LC-MS/MS and higher VDZ levels during IV therapy were associated with higher VDZ serum levels during SC therapy. Active smoking and prior use of >1 biologic and/or tofacitinib were associated with lower VDZ levels during SC therapy (table 1). A VDZ trough concentration of ≥ 34.5 µg/mL during SC maintenance therapy predicted corticosteroid free clinical remission with a sensitivity, specificity, positive predictive value and negative predictive value of 60%, 75%, 86% and 43%, respectively. Conclusion VDZ serum concentrations were significantly higher during SC therapy versus IV treatment. A VDZ trough concentrations ≥ 34.5 µg/mL was associated with corticosteroid free remission.