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OP029 Drug-concentration versus symptom-driven dose adaptation of Infliximab in patients with active Crohns disease: a prospective, randomised, multicentre trial (Tailorix)

The most potent available treatment for active Crohn’s disease (CD) is a combination of infliximab (IFX) and azathioprine, leading to disappearance of ulcerations in up to 50% of patients. Because superior outcomes have been associated with serum drug concentrations within what is considered a ‘therapeutic window’, we hypothesised that prospective therapeutic drug monitoring (TDM) would lead to higher remission rates as compared with pure symptom-based dose adaptations.

This was a prospective randomised, double-blinded, multicentre controlled trial in which biologic naïve adult patients with active CD (CDAI > 220, serum CRP > 5 mg/L, and/or faecal calprotectin > 250 µg/g and endoscopic ulcerations) received induction treatment with 3 infusions of IFX 5 mg/kg in combination with azathioprine 2–2.,5 mg/kg/day or MTX in case of intolerance. At week 14, patients were randomised to 1 of 3 different maintenance strategies: 1) dose intensification of IFX in (maximally 2) steps of 2,5 mg/kg based on clinical symptoms, biomarker analysis and serum IFX concentrations drawn before the previous infusion (group 1); 2) dose intensification of IFX from 5 to 10 mg/kg based on the same criteria (group 2), and 3) IFX dose increase to 10 mg/kg based on clinical symptoms alone (group 3). The primary endpoint of the trial was sustained steroid-free clinical remission from week 22 to -54 and absence of ulceration at 1 year based on centrally read endoscopies. Target for IFX dosing was a trough concentration > 3 ug/ml. (EUDRACT NUMBER: 2011-003038-14)

At 27 sites in Belgium, France, and the Netherlands,167 patients were screened, and 122 were randomised (71 F, median age 29.8 years). The 3 groups had comparable patient characteristics. The primary endpoint based on local endoscopy reads was attained in 21/45 (47%) in group 1, 14/37 (38%) in group 2, and 16/40 (40%) in group 3 (p = NS). The proportions of patients without ulcerations at week 54 were 36%, 43%, and 48% (p = NS) and with endoscopic remission (CDEIS < 3) 49%, 51%, and 45% (p = NS). Dose intensification was done in 51%, 65%, and 40% of the patients.

In this prospective randomised exploratory trial in patients with active CD, proactive trough-level–based dose intensification was not superior to dose intensification based on symptoms alone. Results with centrally read endoscopy are being awaited, as well as detailed pharmacokinetic, immunogenicity, and biomarker analysis. More benefit from TDM may be obtained during induction and in dose reduction efforts, which was not studied in this trial.

G. D’Haens*1, S. Vermeire2, G. Lambrecht3, F. Baert4, P. Bossuyt5, M. Nachury6, A. Buisson7, Y. Bouhnik8, J. Filippi9, J. vande Woude10, P. Van Hootegem11, J. Moreau12, E. Louis13, D. Franchimont14, M. De Vos15, F. Mana16, L. Peyrin-Biroulet17, H. Brixi18, M. Allez19, P. Caenepeel20, A. Aubourg21, B. Oldenburg22, M. Pierik23, A. Gils24, S. Chevret25, D. Laharie26

1Academic Medical Centre, Gastroenterology, Amsterdam, Netherlands, 2University Hospitals Gasthuisberg, Gastroenterology, Leuven, Belgium, 3AZ Damiaan, Oostende, Belgium, 4AZ Delta, Roeselare, Belgium, 5Imelda GI Clinical Research Centre, Bonheiden, Belgium, 6Hopital Claude Hurriez, Lille, France, 7Hopital Estaing, Clermont-Ferrand, France, 8Hopital Beaujon, Clichy, France, 9Hospital Archet, Nice, France, 10Erasmus Medical Centre, Rotterdam, Netherlands, 11St Lukas Hospital, Bruges, Belgium, 12Hopital Rangueil, Toulouse, France, 13Hopital Sart Tilman, Liège, Belgium, 14Hopital Erasme, Brussels, Belgium, 15University of Ghent, Ghent, Belgium, 16Free University of Brussels, Brussels, Belgium, 17Hopital Brabois, Nancy, France, 18Hopital Robert Debre, Reims, France, 19Hopital St Louis, Paris, France, 20Ziekenhuis Oost Limburg, Genk, Belgium, 21Hopital Trousseau, Tours, France, 22University of Utrecht, Utrecht, Netherlands, 23University Hospital Maastricht, Maastricht, Netherlands, 24University of Leuven, Leuven, Belgium, 25Dept Biostatistique St Louis, Paris, France, 26Haut-Leveque, Pessac, France