A Matrix-based Model Predicts Primary Response to Infliximab in Crohn's Disease

被引:51
作者
Billiet, Thomas [1 ]
Papamichael, Konstantinos [1 ]
de Bruyn, Magali [1 ,2 ]
Verstockt, Bram [1 ]
Cleynen, Isabelle [1 ]
Princen, Fred [3 ]
Singh, Sharat [3 ]
Ferrante, Marc [4 ]
Van Assche, Gert [4 ]
Vermeire, Severine [4 ]
机构
[1] Katholieke Univ Leuven, Dept Clin & Expt Med, Translat Res Ctr GastroIntestinal Disorders TARGI, Leuven, Belgium
[2] Katholieke Univ Leuven, Dept Microbiol & Immunol, Rega Inst Med Res, Leuven, Belgium
[3] Prometheus Labs, Dept Res & Dev, San Diego, CA USA
[4] Univ Ziekenhuis Leuven, Dept Gastroenterol, Leuven, Belgium
关键词
Anti-TNF; Crohn's disease; primary non-response; INFLAMMATORY-BOWEL-DISEASE; LONDON POSITION STATEMENT; COLITIS ORGANIZATION; ULCERATIVE-COLITIS; BIOLOGICAL THERAPY; EUROPEAN CROHNS; WORLD CONGRESS; IBD; GASTROENTEROLOGY; POLYMORPHISM;
D O I
10.1093/ecco-jcc/jjv156
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: Prediction of primary non-response [PNR] to anti-tumour necrosis factors [TNFs] in inflammatory bowel disease [IBD] is direly needed to select the optimal therapeutic class for a given patient. We developed a matrix-based prediction tool to predict response to infliximab [IFX] in Crohn's disease [CD] patients. Methods: This retrospective single-centre study included 201 anti-TNF naive CD patients who started with IFX induction therapy. PNR occurred in 16 [8%] patients. Clinical, biological [including serum TNF and the IBD serology 6 panel and genetic [the 163 validated IBD risk loci] markers were collected before start. Based on the best fitted regression model, probabilities of primary response to IFX were calculated and arranged in a prediction matrix tool. Results: Multiple logistic regression withheld three final independent predictors [p < 0.05] for PNR: age at first IFX, {odds ratio (OR) (95% confidence interval [CI] of 1.1 (1.0-1.1)}, body mass index [BMI] (0.86 [0.7-1.0]), and previous surgery (4.4 [1.2-16.5]). The accuracy of this prediction model did not improve when the genetic markers were added (area under the curve [AUC] from 0.80 [0.67-0.93] to 0.78 [0.65-0.91]). The predicted probabilities for PNR to IFX increased from 1% to 53% depending on the combination of final predictors. Conclusions: Readily available clinical factors [age at first IFX, BMI, and previous surgery] outperform serological and IBD risk loci in prediction of primary response to infliximab in this real-life cohort of CD patients. This matrix tool could be useful for guiding physicians and may avoid unnecessary or inappropriate exposure to IFX in IBD patients unlikely to benefit.
引用
收藏
页码:1120 / 1126
页数:7
相关论文
共 29 条
[1]   The Use of Prognostic Factors in Inflammatory Bowel Diseases [J].
Billiet T. ;
Ferrante M. ;
Van Assche G. .
Current Gastroenterology Reports, 2014, 16 (11) :1-14
[2]   Targeting TNF-α for the treatment of inflammatory bowel disease [J].
Billiet, Thomas ;
Rutgeerts, Paul ;
Ferrante, Marc ;
Van Assche, Gert ;
Vermeire, Severine .
EXPERT OPINION ON BIOLOGICAL THERAPY, 2014, 14 (01) :75-101
[3]   Detection of infliximab levels and anti-infliximab antibodies: a comparison of three different assays [J].
Casteele, N. Vande ;
Buurman, D. J. ;
Sturkenboom, M. G. G. ;
Kleibeuker, J. H. ;
Vermeire, S. ;
Rispens, T. ;
van der Kleij, D. ;
Gils, A. ;
Dijkstra, G. .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2012, 36 (08) :765-771
[4]   Estimation of ten-year risk of fatal cardiovascular disease in Europe:: the SCORE project [J].
Conroy, RM ;
Pyörälä, K ;
Fitzgerald, AP ;
Sans, S ;
Menotti, A ;
De Backer, G ;
De Bacquer, D ;
Ducimetière, P ;
Jousilahti, P ;
Keil, U ;
Njolstad, I ;
Oganov, RG ;
Thomsen, T ;
Tunstall-Pedoe, H ;
Tverdal, A ;
Wedel, H ;
Whincup, P ;
Wilhelmsen, L ;
Graham, IM .
EUROPEAN HEART JOURNAL, 2003, 24 (11) :987-1003
[5]   Promise and pitfalls of the Immunochip [J].
Cortes, Adrian ;
Brown, Matthew A. .
ARTHRITIS RESEARCH & THERAPY, 2011, 13 (01)
[6]   The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD With the European Crohn's and Colitis Organization: When to Start, When to Stop, Which Drug to Choose, and How to Predict Response [J].
D'Haens, Geert R. ;
Panaccione, Remo ;
Higgins, Peter D. R. ;
Vermeire, Severine ;
Gassull, Miquel ;
Chowers, Yehuda ;
Hanauer, Stephen B. ;
Herfarth, Hans ;
Hommes, Daan W. ;
Kamm, Michael ;
Lofberg, Robert ;
Quary, A. ;
Sands, Bruce ;
Sood, A. ;
Watermayer, G. ;
Lashner, Bret ;
Lemann, Marc ;
Plevy, Scott ;
Reinisch, Walter ;
Schreiber, Stefan ;
Siegel, Corey ;
Targan, Stephen ;
Watanabe, M. ;
Feagan, Brian ;
Sandborn, William J. ;
Colombel, Jean Frederic ;
Travis, Simon .
AMERICAN JOURNAL OF GASTROENTEROLOGY, 2011, 106 (02) :199-212
[7]   Patient Factors That Increase Infliximab Clearance and Shorten Half-life in Inflammatory Bowel Disease: A Population Pharmacokinetic Study [J].
Dotan, Iris ;
Ron, Yulia ;
Yanai, Henit ;
Becker, Stuart ;
Fishman, Sigal ;
Yahav, Lior ;
Ben Yehoyada, Merav ;
Mould, Diane R. .
INFLAMMATORY BOWEL DISEASES, 2014, 20 (12) :2247-2259
[8]   Obesity in Inflammatory Bowel Disease: A Marker of Less Severe Disease [J].
Flores, Avegail ;
Burstein, Ezra ;
Cipher, Daisha J. ;
Feagins, Linda A. .
DIGESTIVE DISEASES AND SCIENCES, 2015, 60 (08) :2436-2445
[9]   Systematic review with meta-analysis: inflammatory bowel disease in the elderly [J].
Gisbert, J. P. ;
Chaparro, M. .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2014, 39 (05) :459-477
[10]   Increased Body Mass Index Is Associated with Earlier Time to Loss of Response to Infliximab in Patients with Inflammatory Bowel Disease [J].
Harper, Jason W. ;
Sinanan, Mika N. ;
Zisman, Timothy L. .
INFLAMMATORY BOWEL DISEASES, 2013, 19 (10) :2118-2124