Thomas Billiet1, Konstantinos Papamichael1, Magali de Bruyn2, Bram Verstockt1, Isabelle Cleynen1, Fred Princen3, Sharat Singh3, Marc Ferrante4, Gert Van Assche4, Severine Vermeire5. 1. Translational Research Center for GastroIntestinal Disorders [TARGID], Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium. 2. Translational Research Center for GastroIntestinal Disorders [TARGID], Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium. 3. Department of Research and Development, Prometheus Laboratories, San Diego, CA, USA. 4. Department of Gastroenterology, Universitair ziekenhuis Leuven, Leuven, Belgium. 5. Department of Gastroenterology, Universitair ziekenhuis Leuven, Leuven, Belgium severine.vermeire@uzleuven.be.
Abstract
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 naïve 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.
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 naïve CDpatients 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 CDpatients. This matrix tool could be useful for guiding physicians and may avoid unnecessary or inappropriate exposure to IFX in IBD patients unlikely to benefit.
Authors: Parambir S Dulai; Brigid S Boland; Siddharth Singh; Khadija Chaudrey; Jenna L Koliani-Pace; Gursimran Kochhar; Malav P Parikh; Eugenia Shmidt; Justin Hartke; Prianka Chilukuri; Joseph Meserve; Diana Whitehead; Robert Hirten; Adam C Winters; Leah G Katta; Farhad Peerani; Neeraj Narula; Keith Sultan; Arun Swaminath; Matthew Bohm; Dana Lukin; David Hudesman; John T Chang; Jesus Rivera-Nieves; Vipul Jairath; G Y Zou; Brian G Feagan; Bo Shen; Corey A Siegel; Edward V Loftus; Sunanda Kane; Bruce E Sands; Jean-Frederic Colombel; William J Sandborn; Karen Lasch; Charlie Cao Journal: Gastroenterology Date: 2018-05-30 Impact factor: 22.682