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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

Background

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

Methods

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.

Results

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).

Conclusion

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.