P334. Concentration–effect relationship of infliximab in Crohn's disease: Results of a cohort study
C. Lamblin1, A. Aubourg1, D. Ternant2, L. Picon1, T. Lecomte1, G. Paintaud2
1CHU Tours, Hepatogastroenterology, Tours, France; 2Université François Rabelais, CNRS 6239 GICC, Tours, France
Background: Infliximab (IFX) has dramatically changed the management of Crohn's disease. Although it has a proven efficacy in inducing and maintaining remission, loss of response is frequently observed, requiring optimisation. Previous studies were in favor of the measurement of IFX trough concentrations to help therapeutic decisions. The aim of our study was to study concentration–effect relationships of IFX in a cohort of Crohn's disease patients.
Methods: All patients with luminal and/or perineal Crohn's disease with maintenance IFX treatment followed between January 2007 and June 2010 in the Hepatogastroenterology Department of Tours University Hospital were included. Crohn's Disease Activity Index (CDAI), serum concentration of C‑reactive protein (CRP) and IFX trough concentration were measured prospectively in a routine clinical manner. Other demographic and clinical data were collected retrospectively. Because of a large variability in the number of IFX concentrations per patient, statistical analyses were performed using the nearer steady-state concentration for each patient. Concentration–effect relationship modeling used Winnonlin® software (Pharsight corp.).
Results: Forty-four patients were included. At the time of analysis, 20 patients were in clinical and biological remission and 24 were in relapse. IFX concentrations were significantly higher in patients in remission than in those relapsing, 6.33 mg/L vs 3.39 mg/L (p < 0.02). No significant association was found between IFX concentrations and concomitant immunosuppressive treatment or presence of antibodies to infliximab. The relationship between CRP and IFX concentrations was best described by an Emax inhibition model: estimated EC50, which is the concentration of infliximab leading to a 50% decrease of CRP concentration, was 1.1 mg/L. According to this model, concentration of CRP below 5 mg/L was obtained by IFX concentrations above 5.6 mg/L.
Relationship between C-reactive protein concentrations and infliximab trough concentration. Observed data are represented by open circles and model-predicted data are represented by the curve.
Conclusions: Our study quantifies the concentration–effect relationhip of IFX in Crohn's disease and suggests an optimal trough concentration of around 5 mg/L.