Adequate Infliximab Exposure During Induction Predicts Remission in Paediatric Patients With Inflammatory Bowel Disease

被引:40
作者
van Hoeve, Karen [1 ,2 ]
Dreesen, Erwin [3 ]
Hoffman, Ilse [1 ]
Van Assche, Gert [2 ,4 ]
Ferrante, Marc [2 ,4 ]
Gils, Ann [3 ]
Vermeire, Severine [2 ,4 ]
机构
[1] Univ Hosp Leuven, Dept Paediat Gastroenterol & Hepatol & Nutr, Leuven, Belgium
[2] Katholieke Univ Leuven, TARGID, Dept Chron Dis Metab & Ageing CHROMETA, Leuven, Belgium
[3] Katholieke Univ Leuven, Lab Therapeut & Diagnost Antibodies, Dept Pharmaceut & Pharmacol Sci, Leuven, Belgium
[4] Katholieke Univ Leuven, Dept Gastroenterol & Hepatol, Univ Hosp Leuven, Leuven, Belgium
关键词
children; inflammatory bowel disease; infliximab; outcome; therapeutic drug monitoring; COLITIS ACTIVITY INDEX; ANTI-TNF THERAPY; CROHNS-DISEASE; TROUGH LEVELS; MAINTENANCE THERAPY; SUSTAINED RESPONSE; CLINICAL-USE; CHILDREN; ANTIBODIES; EXPERIENCE;
D O I
10.1097/MPG.0000000000002265
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Objectives: Therapeutic drug monitoring has been proposed as a useful tool in the management of infliximab (IFX) treated patients with inflammatory bowel disease. The aim of this retrospective study was to determine whether IFX trough levels after induction therapy are predictive for outcome at week 52. Methods: All pediatric patients with inflammatory bowel disease receiving maintenance IFX at our centre, with IFX trough level available at their first maintenance infusion and a follow-up of at least 52 weeks were included. IFX induction regimens could be intensified at the discretion of the treating physician. All children received proactive drug monitoring during maintenance with dose adaptation aiming to target a therapeutic window of 3 to 7 mu g/mL. Results: We included 35 children (23 with Crohn disease and 12 with ulcerative colitis). Median IFX trough levels just before the first maintenance infusion were significantly higher in children achieving clinical (4.6 mu g/mL [2.7-11.8] vs 1.5 mu g/mL[0.9-3.0]), biological (4.6 mu g/mL[2.5-10.3] vs 2.6 mu g/mL[0.3-3.2]) and combined clinical/biological remission (6.0 mu g/mL [3.2-12.0] vs 2.6 mu g/mL [1.1-3.2]) at week 52 compared to children not meeting these criteria (all P <= 0.002). Binary logistic regression identified these trough levels as the only predictor for the same outcomes with an odds ratio (95% confidence interval) of 2.083 (1.085-3.998), 2.203 (1.101-4.408), and 2.264 (1.096-4.680), respectively (all P < 0.05). Conclusions: Adequate IFX exposure during induction therapy is associated with better clinical and/or biological remission at week 52. Postinduction IFX trough levels were the only predictor for clinical and/or biological remission at week 52.
引用
收藏
页码:847 / 853
页数:7
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共 50 条
[1]   Pharmacokinetics of Infliximab in Children with Moderate-to-Severe Ulcerative Colitis: Results from a Randomized, Multicenter, Open-label, Phase 3 Study [J].
Adedokun, Omoniyi J. ;
Xu, Zhenhua ;
Padgett, Lakshmi ;
Blank, Marion ;
Johanns, Jewel ;
Griffiths, Anne ;
Ford, Joyce ;
Zhou, Honghui ;
Guzzo, Cynthia ;
Davis, Hugh M. ;
Hyams, Jeffrey .
INFLAMMATORY BOWEL DISEASES, 2013, 19 (13) :2753-2762
[2]   Prognostic factors for long-term infliximab treatment in Crohn's disease patients: a 20-year single centre experience [J].
Billiet, T. ;
Cleynen, I. ;
Ballet, V. ;
Ferrante, M. ;
Van Assche, G. ;
Gils, A. ;
Vermeire, S. .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2016, 44 (07) :673-683
[3]   Infliximab trough levels and persistent vs transient antibodies measured early after induction predict long-term clinical remission in patients with inflammatory bowel disease [J].
Bodini, Giorgia ;
Giannini, Edoardo G. ;
Savarino, Vincenzo ;
Del Nero, Lorenzo ;
Lo Pumo, Sara ;
Brunacci, Matteo ;
De Bortoli, Nicola ;
Jain, Anjali ;
Tolone, Salvatore ;
Savarino, Edoardo .
DIGESTIVE AND LIVER DISEASE, 2018, 50 (05) :452-456
[4]   Secondary Loss of Response to Infliximab in Pediatric Crohn Disease: Does It Matter How and When We Start? [J].
Bolia, Rishi ;
Rosenbaum, Jeremy ;
Schildkraut, Vered ;
Hardikar, Winita ;
Oliver, Mark ;
Cameron, Donald ;
Alex, George .
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, 2018, 66 (04) :637-640
[5]   Infliximab trough levels may predict sustained response to infliximab in patients with Crohn's disease [J].
Bortlik, Martin ;
Duricova, Dana ;
Malickova, Karin ;
Machkova, Nadezda ;
Bouzkova, Eva ;
Hrdlicka, Ludek ;
Komarek, Arnost ;
Lukas, Milan .
JOURNAL OF CROHNS & COLITIS, 2013, 7 (09) :736-743
[6]  
Burgess CJ, 2018, ARCH DIS CHILD
[7]   Therapeutic Drug Monitoring in Pediatric Inflammatory Bowel Disease [J].
Carman N. ;
Mack D.R. ;
Benchimol E.I. .
Current Gastroenterology Reports, 2018, 20 (5)
[8]   The Impact of Combination Therapy on Infliximab Levels and Antibodies in Children and Young Adults With Inflammatory Bowel Disease [J].
Chi, Lisa Yue ;
Zitomersky, Naamah Levy ;
Liu, Enju ;
Tollefson, Sophia ;
Bender-Stern, Julia ;
Naik, Snehal ;
Snapper, Scott ;
Bousvaros, Athos .
INFLAMMATORY BOWEL DISEASES, 2018, 24 (06) :1344-1351
[9]   Clinical Use of Measuring Trough Levels and Antibodies against Infliximab in Patients with Pediatric Inflammatory Bowel Disease [J].
Choi, So Yoon ;
Kang, Ben ;
Lee, Jee Hyun ;
Choe, Yon Ho .
GUT AND LIVER, 2017, 11 (01) :55-61
[10]   Biological Therapy in Pediatric Inflammatory Bowel Disease A Systematic Review [J].
Corica, Domenico ;
Romano, Claudio .
JOURNAL OF CLINICAL GASTROENTEROLOGY, 2017, 51 (02) :100-110