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P475. Infliximab concentration is associated with mucosal healing in intestinal bowel disease (IBD)

S. Paul1, E. Del Tedesco1, H. Marotte1, M. Rinaudo-Gaujous1, J.M. Phelip1, L. Peyrin-Biroulet2, X. Roblin1, 1University of Saint Etienne, France, 2Nancy, France


For the first time, relationship between infliximab concentration and mucosal healing (HM) is evaluated in IBD, after therapeutic optimisation.


We included, in a prospective study, all IBD subjects in infliximab (IFX) failure at 5 mg/kg, after a primary response. A clinical relapse was defined by a CDAI >220, a faecal calprotectin >400–µg/g and a C reactive protein >10 mg/l in CD. In UC, clinical relapse was considered when the Mayo score was >7 with a Mayo endoscopic subscore >1. An increment of the dose to 10 mg/kg IFX was managed in all patients. IFX concentration and ATI were evaluated from serum samples drawn before therapeutic “optimisation” and at week 8. C reactive protein and faecal calprotectin were measured the day of optimization and at week 8 for patients with Crohn's disease. A rectosigmoidoscopy was performed the day of optimisation and at week 8 for patients with UC. HM was defined by a faecal calprotectin <250 µg/g and a C reactive protein <5 mg/L in Crohn's disease. In UC, a Mayo endoscopic subscore <2 defined HM.


We included 52 patients (mean age: 32.1 years, sex ratio: M/F: 0.9, 34 CD). After optimisation, 50% achieved HM, irrespective of intestinal bowel disease type. Increment of IFX concentration (delta IFX, microg/mL) after therapeutic optimization was significantly associated with mucosal healing (irrespective of intestinal bowel disease type). Rates of healing mucosa were significantly increased between the four quartiles (0%, 7%, 30%, and 70%, respectively; P = 0.001). A delta IFX >0.5 µg/mL was associated with HM (Sensitivity: 0.88, Specificity: 0.77, PPV: 0.79, NPV: 0.87; p = 0.0001, AUROC: 0.89). Delta IFX median (µg/mL) was respectively, with or without HM, in IBD (+2.2 vs −0.2, p < 0.0001). Infliximab concentration <2 µg/mL before increment of dose to 10 mg/kg IFX, without ATI against IFX beyond 200 ng/mL had a strong predictive value for HM achievement after therapeutic optimization whatever the type of IBD.

On multivariate analysis, the only factor associated with HM after optimization was a delta IFX >0.5 µg/ml (LHR = 2.02, 95% CI: 1.01–4.08; p = 0.048. There was a strong tendency between IFX <2 before optimization and HM: LHR = 5.3, 95% CI: 0.82–34.2; p = 0.08).


An increment of IFX after “optimization” is significantly associated with HM in IBD, irrespective of type. IFX trough levels and ATI evaluated before therapeutic optimization had a strong predictive value for HM.