Infliximab and Tumour Necrosis Factor Alpha Measurement on Intestinal Mucosa: A New Tool for the Clinic?

Abstract

Background: Infliximab (IFX) trough levels measurement could partially explain mechanisms of loss in response to this drug. However, little information exists on its concentration at the mucosal level or mucosal pharmacokinetics. Objective: The aim of this study was to investigate whether IFX could be measured within intestinal mucosa, and whether a correlation between mucosal level, serum level, and clinical response could be hypothesised. Methods: Fifteen consecutive patients with inflammatory bowel disease receiving stable doses of IFX who underwent endoscopy were enrolled. Biopsies were taken from an affected and an unaffected area and cultured for 48 hours, and serum samples were also collected. IFX and tumour necrosis factor alpha (TNF-α) levels were measured using commercially available enzyme-linked immunosorbent assay kits. Results: IFX levels were detected in 80% of the colonic biopsy supernatants and in 60% of the serum samples. TNF-α intestinal mucosal levels were detectable in 100% of patients, while TNF-α serum levels were detectable in 75%. Mucosal and serum levels of IFX and TNF-α did not correlate; no correlation was found between the last infusion and serum or intestinal mucosal levels. Levels of IFX were more frequently undetectable in the mucosa of patients not responding to IFX therapy. Conclusions: Detectable levels of IFX and TNF-α can be found in intestinal mucosa. IFX mucosa levels could be useful to stratify patients into responders and non-responders to IXF therapy.