P590 Which biomarkers have an effect on therapeutic vedolizumab drug levels? A retrospective analysis from a London Tertiary Centre.
Bancil, A.(1);Stevens, M.(2);Kok, K.(1);
(1)The Royal London Hospital, Department of Gastroenterology, London, United Kingdom;(2)The Royal London Hospital, Department of Immunology, London, United Kingdom
Background
Vedolizumab is a humanised monoclonal antibody that binds to the α4β7 integrin and is an established treatment for both Crohn’s Disease (CD) and Ulcerative Colitis (UC). Drug levels for anti-tumour necrosis factor-α inhibitors such as infliximab and adalimumab have been used routinely for therapeutic drug monitoring (TDM). Target therapeutic levels for vedolizumab are yet to be established. Correlations with vedolizumab levels have been found in prospective and retrospective studies with a number of biomarkers such as C-Reactive Protein (CRP), albumin and Body Mass Index (BMI). However, these have failed to replicate consistently among studies of vedolizumab drug levels.
Methods
Trough serum vedolizumab drug levels were taken for 81 patients through a period of 3 months. These were analysed using a drug tolerant assay (IDKMonitor Drug level ELISA and IDKMonitor vedolizumab Free anti-drug antibody ELISA) run on a Dynex DS2 ELISA processor. These were collected from 33 CD patients, 46 UC patients and 2 patients with unclassified Inflammatory Bowel Disease (IBD-U). Faecal calprotectin (FCP) was collected in a subset of patients. Serum CRP, albumin, and haemoglobin (Hb) levels were also taken alongside levels. BMI was recorded at our infusion unit before receiving the infusion.
Results
81 patients had drug levels taken: CD patients (mean drug level Q8w - 7.8 mcg/ml, Q4w - 18.6 mcg/ml, 9 patients with concomitant immunomodulators (CIM)), UC patients (mean drug level Q8w - 9.4 mcg/ml, Q4w – 22.0 mcg/ml, 5 patients with CIM), IBD-U (mean drug level Q8w - 15.2 mcg/ml, no patients with CIM). One patient developed anti-drug antibodies. Correlation was analysed using simple linear regression. A positive correlation was found with vedolizumab levels and albumin (correlation coefficient (r) = 0.11; p=0.03) but not with CRP (p=0.49), Hb (p=0.56), BMI (p=0.33) or FCP (p=0.08).
Conclusion
Our results indicate that albumin positively correlates with a higher vedolizumab drug level, which suggests that drug levels will be lower and perhaps less effective in patients with a low albumin level. Further studies should look at larger numbers of patients to identify whether the correlations identified with other biomarkers are significant and identify therapeutic target levels for vedolizumab. These will help guide TDM for patients and inform clinicians of when to switch as well as recognising likely non-responders and thus provide a personalised approach to biologic choice.