Claire Liefferinckx1, Jérémie Bottieau2, Jean-François Toubeau2, Debby Thomas3, Jean-François Rahier4, Edouard Louis5, Filip Baert6, Pieter Dewint7,8, Lieven Pouillon9, Guy Lambrecht10, François Vallée2, Severine Vermeire11, Peter Bossuyt9, Denis Franchimont1. 1. Department of Gastroenterology, Hôpital Erasme, ULB, Brussels, Belgium. 2. Department of Electrical Engineering, University of Mons, Mons, Belgium. 3. Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium. 4. Department of Gastroenterology, CHU UCL Namur, Yvoir, Belgium. 5. Department of Gastroenterology, Centre Hospitalier Universitaire Sart-Tilman, ULG, Liège, Belgium. 6. Department of Gastroenterology, AZ Delta, Roeselare-Menen-Torhout, Belgium. 7. Department of Gastroenterology, AZ Maria Middelares, Ghent, Belgium. 8. Department of Gastroenterology, UZ Antwerp, Antwerp, Belgium. 9. Department of Gastroenterology, Imelda General Hospital, Bonheiden, Belgium. 10. Department of Gastroenterology, AZ Damiaan, Oostende, Belgium. 11. Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.
Abstract
BACKGROUND: The loss of response to infliximab is a challenge for clinicians in the management of inflammatory bowel disease (IBD). Mounting evidence suggests that therapeutic drug monitoring at induction may predict remission during maintenance. The aim of the study was to improve predictive models of remission by exploring new peak and intermediate infliximab measurements during induction. METHODS: This was a prospective multicenter study evaluating the pharmacokinetics of infliximab during induction in a pioneer cohort of 63 patients with IBD. Pharmacokinetics data including peak, intermediate, and trough levels were combined with clinical and biological parameters and were subsequently fed into tailored logistic regression and tree-based techniques to predict remission at week 30. RESULTS: Infliximab peak levels at week 2, intermediate levels at week 3, and trough levels at week 6 were correlated with remission at week 30. Predictive models exhibited an increased accuracy over the successive timepoints of the induction with key inputs such as albumin, C-reactive protein, eosinophils, neutrophils, lymphocytes, intermediate level at week 3, trough level at week 6, and age at diagnosis. Our predictive model of remission at week 30 was obtained with an area under the receiver operating characteristic curve of 0.9 ± 0.12, a sensitivity of 89%, and a specificity of 75%. CONCLUSIONS: This study showed the clinical relevance of measuring new infliximab levels to predict remission in patients with IBD. These findings lay the foundation for a personalized medicine in which biotherapies could be monitored at an early stage, thereby improving patients' clinical management.
BACKGROUND: The loss of response to infliximab is a challenge for clinicians in the management of inflammatory bowel disease (IBD). Mounting evidence suggests that therapeutic drug monitoring at induction may predict remission during maintenance. The aim of the study was to improve predictive models of remission by exploring new peak and intermediate infliximab measurements during induction. METHODS: This was a prospective multicenter study evaluating the pharmacokinetics of infliximab during induction in a pioneer cohort of 63 patients with IBD. Pharmacokinetics data including peak, intermediate, and trough levels were combined with clinical and biological parameters and were subsequently fed into tailored logistic regression and tree-based techniques to predict remission at week 30. RESULTS: Infliximab peak levels at week 2, intermediate levels at week 3, and trough levels at week 6 were correlated with remission at week 30. Predictive models exhibited an increased accuracy over the successive timepoints of the induction with key inputs such as albumin, C-reactive protein, eosinophils, neutrophils, lymphocytes, intermediate level at week 3, trough level at week 6, and age at diagnosis. Our predictive model of remission at week 30 was obtained with an area under the receiver operating characteristic curve of 0.9 ± 0.12, a sensitivity of 89%, and a specificity of 75%. CONCLUSIONS: This study showed the clinical relevance of measuring new infliximab levels to predict remission in patients with IBD. These findings lay the foundation for a personalized medicine in which biotherapies could be monitored at an early stage, thereby improving patients' clinical management.
Authors: Jurij Hanzel; Laura H Bukkems; Krisztina B Gecse; Geert R D'Haens; Ron A A Mathôt Journal: Aliment Pharmacol Ther Date: 2021-09-24 Impact factor: 9.524