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

被引:43
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
相关论文
共 50 条
[11]   Postinduction serum infliximab trough level and decrease of C-reactive protein level are associated with durable sustained response to infliximab: a retrospective analysis of the ACCENT I trial [J].
Cornillie, Freddy ;
Hanauer, Stephen B. ;
Diamond, Robert H. ;
Wang, Jianping ;
Tang, Kezhen L. ;
Xu, Zhenhua ;
Rutgeerts, Paul ;
Vermeire, Severine .
GUT, 2014, 63 (11) :1721-1727
[12]   Therapeutic drug monitoring was helpful in guiding the decision-making process for children receiving infliximab for inflammatory bowel disease [J].
Deora, Vini ;
Kozak, Justin ;
El-Kalla, Mohamed ;
Huynh, Hien Q. ;
El-Matary, Wael .
ACTA PAEDIATRICA, 2017, 106 (11) :1863-1867
[13]   Pharmacokinetic Properties of Infliximab in Children and Adults with Crohn's Disease: A Retrospective Analysis of Data from 2 Phase III Clinical Trials [J].
Fasanmade, Adedigbo A. ;
Adedokun, Omoniyi J. ;
Blank, Marion ;
Zhou, Honghui ;
Davis, Hugh M. .
CLINICAL THERAPEUTICS, 2011, 33 (07) :946-964
[14]   Clinical course and outcomes of diagnosing Inflammatory Bowel Disease in children 10 years and under: retrospective cohort study from two tertiary centres in the United Kingdom and in Italy [J].
Gasparetto, Marco ;
Guariso, Graziella ;
Dalla Pozza, Laura Visona' ;
Ross, Alexander ;
Heuschkel, Robert ;
Zilbauer, Matthias .
BMC GASTROENTEROLOGY, 2016, 16
[15]   Combining Therapeutic Drug Monitoring with Biosimilars, a Strategy to Improve the Efficacy of Biologicals for Treating Inflammatory Bowel Diseases at an Affordable Cost [J].
Gils, Ann .
DIGESTIVE DISEASES, 2017, 35 (1-2) :61-68
[16]   Prediction of Short- and Medium-term Efficacy of Biosimilar Infliximab Therapy. Do Trough Levels and Antidrug Antibody Levels or Clinical And Biochemical Markers Play the More Important Role? [J].
Gonczi, Lorant ;
Vegh, Zsuzsanna ;
Golovics, Petra Anna ;
Rutka, Mariann ;
Gecse, Krisztina Barbara ;
Bor, Renata ;
Farkas, Klaudia ;
Szamosi, Tamas ;
Bene, Laszlo ;
Gasztonyi, Beata ;
Kristof, Tunde ;
Lakatos, Laszlo ;
Miheller, Pal ;
Palatka, Karoly ;
Papp, Maria ;
Patai, Arpad ;
Salamon, Agnes ;
Toth, Gabor Tamas ;
Vincze, Aron ;
Biro, Edina ;
Lovasz, Barbara Dorottya ;
Kurti, Zsuzsanna ;
Szepes, Zoltan ;
Molnar, Tamas ;
Lakatos, Peter L. .
JOURNAL OF CROHNS & COLITIS, 2017, 11 (06) :697-705
[17]   Predictors of response to Infliximab in children with luminal Crohn's disease [J].
Grover, Zubin ;
Biron, Rebecca ;
Carman, Nicholas ;
Lewindon, Peter .
JOURNAL OF CROHNS & COLITIS, 2014, 8 (08) :739-746
[18]   Infliximab Optimization Based on Therapeutic Drug Monitoring in Pediatric Inflammatory Bowel Disease [J].
Hofmekler, Tatyana ;
Bertha, Madeline ;
McCracken, Courtney ;
Martineau, Benadette ;
McKinnon, Elizabeth ;
Schoen, Bess T. ;
McElhanon, Barbara O. ;
Tenjarla, Gayathri ;
Kugathasan, Subra ;
Sauer, Cary G. .
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, 2017, 64 (04) :580-585
[19]   Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn's disease in children [J].
Hyams, Jeffrey ;
Crandall, Wallace ;
Kugathasan, Subra ;
Griffiths, Anne ;
Olson, Allan ;
Johanns, Jewel ;
Liu, Grace ;
Travers, Suzanne ;
Heuschkel, Robert ;
Markowitz, James ;
Cohen, Stanley ;
Winter, Harland ;
Veereman-Wauters, Gigi ;
Ferry, George ;
Baldassano, Robert .
GASTROENTEROLOGY, 2007, 132 (03) :863-873
[20]   Induction and Maintenance Therapy With Infliximab for Children With Moderate to Severe Ulcerative Colitis [J].
Hyams, Jeffrey ;
Damaraju, Lakshmi ;
Blank, Marion ;
Johanns, Jewel ;
Guzzo, Cynthia ;
Winter, Harland S. ;
Kugathasan, Subra ;
Cohen, Stanley ;
Markowitz, James ;
Escher, Johanna C. ;
Veereman-Wauters, Gigi ;
Crandall, Wallace ;
Baldassano, Robert ;
Griffiths, Anne .
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, 2012, 10 (04) :391-U169