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* = Presenting author

P453 Infliximab population pharmacokinetic modelling in patients with Inflammatory Bowel Disease (IBD): Patient factors influencing infliximab pharmacokinetics

J. Guardiola*1, L. Rodriguez-Alonso1, E. Santacana2, N. Padullés2, H. Colom3, A. Padullés2, C. Arajol1, A. Ruiz-Cerulla1, S. Cobo2, J. Bas4, J. Climent4, F. Morandeira4, F. Rodriguez-Moranta1

1Hospital Universitario de Bellvitge, Gastroenterology, L´Hospitalet de Llobregat, Spain, 2Hospital Universitario de Bellvitge, Pharmacy, L´Hospitalet de Llobregat, Spain, 3Barcelona University, Pharmacokinetics. School of Pharmacy, Barcelona, Spain, 4Hospital Universitario de Bellvitge, Immunology, L´Hospitalet de Llobregat, Spain

Background

There is a high interindividual variability in IFX pharmacokinetics (PK) and trough levels (TLI) in IBD. This is relevant because TLI influence response to therapy. The objective of the study was to evaluate factors affecting IFX exposure and pharmacokinetic variability in IBD.

Methods

Patient data were collected prospectively from patients on IFX between July´13 and March´14. Samples were collected before intravenous infusion at steady state. TLI and antibodies toward infliximab (ATI) were measured by ELISA (Promonitor®). Pharmacokinetic analysis based on the Fasanmade et al. PopPK model for Crohn disease (1) was carried out using Nonmem®7.2. TLI, individual peak levels (Cmax) and area under the concentration-time curve (AUC) were individually predicted and individual PK parameters were calculated (Bayesian approach) according to interindividual variance of the population PK model.

Results

132 TLI and ATI were measured from 64 patients (25 ulcerative colitis, 39 Crohn's disease). TLI, dose-adjusted TLI and dose-adjusted AUC were significantly higher in patients without ATI and in those receiving IMM before initiating IFX. ATI formation was associated with a 26.8% increase in clearance (Cl) (p< 0.00001) whereas Inmunomodulators (IMM) significantly reduced Cl. Patients who initiated IMM before IFX therapy required their first dose escalation later than those who were not on concurrent IMM (p=0.015). When IMM were initiated before IFX, t1/2 was longer than when IMM were added throughout IFX therapy or no prescribed. A higher proportion of patients achieved TLI > 3 mg/L if serum albumin concentration (SAC) was >3.9 g/L. Smoking and SAC<3.9 were associated with an average 162% and 13% increase in Cl, respectively.

Conclusion

Inmunomodulators, SAC, presence of ATI and smoking status influence IFX pharmacokinetics. Patients who initiated IMM before IFX therapy could have better pharmacokinetic profile than patients without IMM or when IMM were added throughout IFX therapy. IFX dosing could be individualized according these variables in order to improve outcomes for IFX-treated patients with IBD.