DOP047 Infliximab exposure predicts superior endoscopic outcomes in patients with active Crohn’s disease: pharmacokinetic–pharmacodynamic analysis of TAILORIX
E. Dreesen1*, G. D'Haens2, F. Baert3, B. Pariente4, Y. Bouhnik5, J. vander Woude6, J. Moreau7, D. Laharie8, S. Vermeire9,10, A. Gils1
1KU Leuven, Departement of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium, 2Academic Medical Centre, Amsterdam, The Netherlands, 3AZ Delta, Roeselare, Belgium, 4Hospital Claude Huriez, Lille, France, 5Hospital Beaujon, Clichy, France, 6Erasmus MC, Rotterdam, The Netherlands, 7CHU, Toulouse, Belgium, 8Hospital Haut-Lévêque, Bordeaux, France, 9University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium, 10KU Leuven, Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium
In the TAILORIX study, “proactive” dose escalation based on infliximab (IFX) serum concentrations (TDM groups) had no added value to “reactive” dose escalation based on symptoms (TDM groups and control group).1 In patients randomised to TDM groups, reactive dose escalation was only allowed in the presence of elevated serum CRP (>5 mg/l) and/or faecal calprotectin (FC, >250 μg/g). We explored the value of pharmacokinetic (PK) and pharmacodynamic (PD) monitoring of IFX therapy in patients with Crohn’s disease (CD) in TAILORIX.
We studied associations between PK markers (IFX concentrations), PD markers (CD activity index or CDAI, CRP and FC) and the endoscopic remission (CD endoscopic index of severity, CDEIS <3), using prospectively collected data from 122 patients with CD in TAILORIX.
During induction therapy, IFX trough concentrations (TC) were significantly higher in patients achieving endoscopic remission by w12 compared with patients who did not (Table 1). An IFX TC ≥23.1 μg/ml at w2 and ≥10.0 μg/ml at w6 predicted endoscopic remission by w12 (
In TAILORIX, a clear exposure-response relation was observed during IFX induction therapy. The additional value of IFX concentration-based dose escalation during maintenance therapy might be blurred due to CDAI based dose escalations that increased the background IFX exposure and response.
1.D'Haens G, Vermeire S, Lambrecht G,