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* = Presenting author

P005 Variability in Vedolizumab Exposure between Patients with Inflammatory Bowel Disease

A. Gils1, E. Dreesen*1, M. Peeters1, E. Brouwers1, M. Ferrante2, G. Van Assche2, S. Vermeire2

1KU Leuven, P.O. Box 820 Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium, 2KU Leuven, P.O. Box 7003, Department of Clinical and Experimental Medicine, Leuven, Belgium

Background

Vedolizumab (VDZ), a humanised monoclonal antibody that specifically targets the α4β7 integrin, has been approved for the treatment of patients with moderate to severe Crohn’s disease (CD) and ulcerative colitis (UC) following successful completion of the GEMINI phase 3 programmes. Nothing is known about the relation between drug exposure and efficacy in real-life practice.

Methods

Enzyme-linked immunosorbent assays for measuring serum VDZ concentrations and anti-drug antibodies (ADAbs) were developed in house. A total of 37 VDZ naïve patients (24 CD; 13 UC) were sampled at trough during induction treatment (300 mg IV administered at weeks 0, 2, and 6). All patients but 1 had prior anti-tumour necrosis factor-alpha exposure. VDZ pharmacokinetics (PK) during induction was described based on trough concentrations and baseline patient factors influencing variability were tested (sex, [lean] body mass, disease type (CD or UC), C-reactive protein (CRP), albumin, and lymphocyte count). Biological response, based on CRP, was correlated to the VDZ serum concentrations.

Results

A substantial interindividual variability in VDZ serum concentrations was observed at week 2 (median 27.5 µg/mL, IQR 15.6 µg/mL) and week 6 (median 24.9 µg/mL, IQR 18.8 µg/mL). Two patients with CD had undetectable VDZ trough concentrations at week 6, of which one had detectable ADAbs. No significant difference in week 2 and 6 trough concentrations was seen between CD or UC. Patients with a baseline CRP above 10 mg/L had a significantly lower VDZ trough concentration at week 2 (p = .03). A baseline serum albumin below 40 g/L was associated with significantly lower VDZ trough concentration at week 6 (p = 0.04). Women had significantly higher VDZ trough concentration at week 2 (p = 0.0005). A significant negative correlation between lean body mass and the VDZ trough concentration at week 2 was found (p = 0.001). Patients who had a decrease in CRP (n = 23, excluding ADAb+ patient) between week 0 and week 6 had significantly higher VDZ trough concentrations at week 6 (median 31.7 µg/mL, IQR 20.8 µg/mL), compared with patients who had an increase in CRP (n = 13) (median 16.4 µg/mL, IQR 10.8 µg/mL) 
(p = .046).

Conclusion

This first real-life experience with VDZ shows substantial PK variability between patients. High CRP and low albumin at baseline, both indicators of disease severity, were shown to predict lower VDZ trough concentrations during induction. Higher (lean) body mass is shown to be associated with lower VDZ trough concentrations at week 2. Early biological response, judged by a decrease in CRP by week 6, is associated with significantly higher VDZ exposure at week 6, already suggesting an early exposure-response correlation.