A Matrix-based Model Predicts Primary Response to Infliximab in Crohn's Disease.
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.
Translational Research Center for GastroIntestinal Disorders [TARGID], Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
Thomas
T
Billiet
Translational Research Center for GastroIntestinal Disorders [TARGID], Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
Konstantinos
K
Papamichael
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.
Magali
M
de Bruyn
Translational Research Center for GastroIntestinal Disorders [TARGID], Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
Bram
B
Verstockt
Translational Research Center for GastroIntestinal Disorders [TARGID], Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
Isabelle
I
Cleynen
Department of Research and Development, Prometheus Laboratories, San Diego, CA, USA.
Fred
F
Princen
Department of Research and Development, Prometheus Laboratories, San Diego, CA, USA.
Sharat
S
Singh
Department of Gastroenterology, Universitair ziekenhuis Leuven, Leuven, Belgium.
Marc
M
Ferrante
Department of Gastroenterology, Universitair ziekenhuis Leuven, Leuven, Belgium.
Gert
G
Van Assche
Department of Gastroenterology, Universitair ziekenhuis Leuven, Leuven, Belgium severine.vermeire@uzleuven.be.
Severine
S
Vermeire
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D000066491:Clinical Decision-Making / Q000379:methods*; D003424:Crohn Disease / Q000188:drug therapy*; D003661:Decision Support Techniques; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
D005765:Gastrointestinal Agents; D000069285:Infliximab
Anti-TNF; Crohn’s disease; primary non-response