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P500. Fecal loss of infliximab as a cause of lack of response in severe inflammatory bowel disease

J.F. Brandse1, M.E. Wildenberg2, J.R. de Bruyn1, G. Wolbink3, M. Lowenberg1, C.Y. Ponsioen1, G.R. van den Brink1, G.R.A.M. D'Haens1, 1Academic Medical Center, Gastroenterology and Hepatology, Amsterdam, Netherlands, 2Tytgat Institute for Liver an Intestinal Research, Amsterdam, Netherlands, 3Sanquin Research Laboratory, Amsterdam, Netherlands

Background

Although Infliximab (IFX) has proven its efficacy both in Crohn's disease (CD) and Ulcerative Colitis (UC), still a considerable group of patients fails to respond to induction therapy. One of the hypotheses behind this phenomenon is increased clearance or loss of the drug.

In severe CD and UC, the mucosa is diffusely denuded and ulcerated, leading to massive loss of proteins, electrolytes and other nutrients. We hypothesized that, even after intravenous administration, IFX may be lost through this ‘leaky gut’. Fecal loss of IFX in this context has not been investigated up to date and this was the focus of the current study.

Methods

In this pilot study we prospectively collected repeated fecal samples of IBD patients within the first 14 days after starting IFX therapy.

Fecal samples were weighed and homogenized in PBS containing bovine serum albumin. Supernatant was collected after centrifugation and tested with a well established ELISA by Sanquin Laboratories to detect the presence of Infliximab.

Clinical response in these patients was assessed 3 months after the initiation of IFX therapy.

Results

9 IBD patients (3 CD, 6 UC) with different disease localizations (5 Ulcerative Pancolitis, 1 Proctitis, 2 Ileocecal CD, 1 Crohn's Colitis) starting on IFX 5 mg/kg at week 0–2-6 were included. One patient (Crohn's colitis) received an extra infusion (5 mg/kg) at day 4 because of initial non response.

IFX could be detected in the feces of all patients. The highest concentrations were measured in the first days after initiation of therapy, meaning in the most acute phase of the disease.

In non responders (3/9) the amount of drug detected in stool at the first day after infusion was significantly (p: 0.024) higher than in patients who had clinical response.

Conclusion

IFX can be detected in the feces of patients with severe IBD, especially short after infusion. This phenomenon may contribute to rapid disappearance of the drug out of the gut and the circulation leading to insufficient response.