Karen van Hoeve1,2, Erwin Dreesen3, Ilse Hoffman1, Gert Van Assche2,4, Marc Ferrante2,4, Ann Gils3, Séverine Vermeire2,4. 1. Department of Paediatric Gastroenterology & Hepatology & Nutrition, University Hospitals Leuven, KU Leuven, Leuven, Belgium. 2. TARGID, Department of Chronic Diseases, Metabolism and Ageing [CHROMETA], KU Leuven, Leuven, Belgium. 3. Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium. 4. Department of Gastroenterology & Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
Abstract
BACKGROUND: The role of therapeutic drug monitoring for infliximab [IFX] therapy in children with inflammatory bowel disease [IBD] is poorly investigated. We determined if IFX exposure correlates with long-term remission in children. METHODS: In this retrospective study, all children with Crohn's disease [CD] and ulcerative colitis [UC], receiving maintenance IFX at our centre, were included. Serum trough levels and cumulative drug exposure were correlated with clinical, biological, and endoscopic remission. All children received proactive drug monitoring and dose adaptation aiming to target a therapeutic window of 3-7 µg/mL. All data are presented as median [interquartile range]. RESULTS: A total of 686 serum levels during IFX maintenance in 52 paediatric patients [33 CD and 19 UC] were included (median 9 [4-18] per patient). With a median of 17 [8-36] months under IFX therapy, 39/52 [75%] patients were in clinical remission and 29/40 [73%] patients were in endoscopic remission. Median IFX trough levels were significantly higher when children achieved clinical remission (5.4 [3.8-8.0] µg/mL versus 4.2 [2.6-6.7] µg/mL), biological remission (5.2 [3.7-7.7] µg/mL versus 4.2 [2.6-6.5] µg/mL), combined clinical and biological remission (5.7 [4.0-8.2] µg/mL versus 4.4 [2.7-6.8] µg/mL) and endoscopic remission (6.5 [4.2-9.5] µg/mL versus 3.2 [2.3-5.6] µg/mL) compared with not meeting these criteria [all p ≤ 0.001]. CONCLUSIONS: In this large paediatric cohort, children with clinical and/or endoscopic remission had significantly higher IFX exposure during maintenance therapy. We showed excellent outcome data using serial and systematic measurements of drug levels. This could provide a rationale for the use of proactive drug monitoring in children in order to improve long-term outcomes.
BACKGROUND: The role of therapeutic drug monitoring for infliximab [IFX] therapy in children with inflammatory bowel disease [IBD] is poorly investigated. We determined if IFX exposure correlates with long-term remission in children. METHODS: In this retrospective study, all children with Crohn's disease [CD] and ulcerative colitis [UC], receiving maintenance IFX at our centre, were included. Serum trough levels and cumulative drug exposure were correlated with clinical, biological, and endoscopic remission. All children received proactive drug monitoring and dose adaptation aiming to target a therapeutic window of 3-7 µg/mL. All data are presented as median [interquartile range]. RESULTS: A total of 686 serum levels during IFX maintenance in 52 paediatric patients [33 CD and 19 UC] were included (median 9 [4-18] per patient). With a median of 17 [8-36] months under IFX therapy, 39/52 [75%] patients were in clinical remission and 29/40 [73%] patients were in endoscopic remission. Median IFX trough levels were significantly higher when children achieved clinical remission (5.4 [3.8-8.0] µg/mL versus 4.2 [2.6-6.7] µg/mL), biological remission (5.2 [3.7-7.7] µg/mL versus 4.2 [2.6-6.5] µg/mL), combined clinical and biological remission (5.7 [4.0-8.2] µg/mL versus 4.4 [2.7-6.8] µg/mL) and endoscopic remission (6.5 [4.2-9.5] µg/mL versus 3.2 [2.3-5.6] µg/mL) compared with not meeting these criteria [all p ≤ 0.001]. CONCLUSIONS: In this large paediatric cohort, children with clinical and/or endoscopic remission had significantly higher IFX exposure during maintenance therapy. We showed excellent outcome data using serial and systematic measurements of drug levels. This could provide a rationale for the use of proactive drug monitoring in children in order to improve long-term outcomes.
Authors: Konstantinos Papamichael; Adam S Cheifetz; Gil Y Melmed; Peter M Irving; Niels Vande Casteele; Patricia L Kozuch; Laura E Raffals; Leonard Baidoo; Brian Bressler; Shane M Devlin; Jennifer Jones; Gilaad G Kaplan; Miles P Sparrow; Fernando S Velayos; Thomas Ullman; Corey A Siegel Journal: Clin Gastroenterol Hepatol Date: 2019-03-27 Impact factor: 11.382
Authors: John L Lyles; Aditi A Mulgund; Laura E Bauman; Weizhe Su; Lin Fei; Deepika L Chona; Puneet Sharma; Renee K Etter; Jennifer Hellmann; Lee A Denson; Phillip Minar; Dana M Dykes; Michael J Rosen Journal: Inflamm Bowel Dis Date: 2021-03-15 Impact factor: 5.325
Authors: Maria M E Jongsma; Dwight A Winter; Hien Q Huynh; Lorenzo Norsa; Seamus Hussey; Kaija-Leena Kolho; Jiri Bronsky; Amit Assa; Shlomi Cohen; Raffi Lev-Tzion; Stephanie Van Biervliet; Dimitris Rizopoulos; Tim G J de Meij; Dror S Shouval; Eytan Wine; Victorien M Wolters; Christine Martinez-Vinson; Lissy de Ridder Journal: Eur J Pediatr Date: 2020-08-19 Impact factor: 3.183