P045 Dried blood spot sampling can facilitate therapeutic drug monitoring of vedolizumab therapy

Abstract

Background: An association between vedolizumab (VDZ) trough concentrations and outcome has been observed in patients with inflammatory bowel diseases. This association was more pronounced in patients with ulcerative colitis (UC) compared with Crohn's disease (CD). We aimed to develop and validate a dried blood spot (DBS) sampling method to facilitate intensive sampling for exploring the pharmacokinetics of VDZ in more detail. Methods: First, DBS were prepared through spotting of 40 μL of whole citrated blood spiked with VDZ (2‐50 μg/ml) onto a Protein Saver Card. Blood was extracted from DBS cards and the extracts were analysed on ELISA. In addition to routine method validation (precision, accuracy, sensitivity, selectivity), DBS‐related parameters including blood volumes, storage stability and impact of haematocrit were also assessed. Second, DBS derived from finger prick and serum samples obtained via venipuncture were taken concurrently at trough from 15 patients (7 UC and 8 CD) on at least one occasion and VDZ concentrations were compared. Statistical analyses were performed using R. Results: Spiking VDZ to citrated whole blood followed by DBS sampling and extraction revealed an average extraction efficiency of 70 ± 2% (n = 23) with an accuracy of 98‐104% and an imprecision of 7‐11% for each concentration analysed. Residual anti‐TNF and antibodies towards anti‐TNF did not impact VDZ concentration whereas the addition of anti‐VDZ antibodies to spiked VDZ samples caused a similar decrease in VDZ concentration in the DBS‐based as in the serum‐based measurements. Blood spot volumes between 15 μL and 50 μL produced comparable results. Storing the DBS papers at room temperature for one month or the extracts at‐20°C for 3 months did not impair DBS recovery (within 80‐120% compared with the first measurements). Median VDZ serum‐to‐DBS ratio of 2.03 (IQR 1.89‐2.01; Spearman's rank rho=0.93, p < 0.0001) was obtained across the therapeutic relevant range (7.5‐39 μg/ml serum concentration, 17‐paired patient samples). DBS‐converted serum concentrations showed no significant differences with analysed serum concentrations (p = 1.00; Figure1). No analytically relevant impact of haematocrit was observed in the range of 33.6% to 48.9%. (Figure presented) Conclusions: VDZ blood concentrations highly correlate with VDZ serum concentrations over a broad concentration range. The developed tool and the derived conversion ratio can be used to perform VDZ monitoring with improved flexibility by sampling at home, patient convenience and robustness.