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

*Silvia Pecere,1 Valentina Petito,1 Arianna Amato,2 Andrea Poscia,3 Alessandro Armuzzi,1 Loris Riccardo Lopetuso,1 Alessandro Sgambato,4 Giovanni Cammarota,1 †Alfredo Papa,1 †Antonio Gasbarrini,1 †Franco Scaldaferri1

1. Internal Medicine Department, Gastroenterology Division,
Catholic University of the Sacred Heart Rome, Rome, Italy
2. Institute of Anesthesia and Resuscitation, University of the Sacred Heart Rome, Rome, Italy
3. Institute of Hygiene, Catholic University of the Sacred Heart Rome, Rome, Italy
4. Institute of Pathology, Catholic University of the Sacred Heart Rome, Rome, Italy
*Correspondence to silvia.pecere@gmail.com
†These authors contributed equally to the manuscript

Disclosure: The authors have declared no conflicts of interest.
Support: This paper was supported by Fondazione di Ricerca in Medicina, Bologna, Italy, and it was made thanks to the Gastroenterology and Endoscopy Unit (nurses and personnels) of Fondazione Policlinico Universitario Agostino Gemelli Hospital (lgo Gemelli 8), Rome, Italy, the Catholic University of  the Sacred Heart, Rome, Italy, and Corinna Berger, Ph.D, Department of Applied Science & Research Products, Immundiagnostik, Bensheim, Germany gave technical support for Elisa of infliximab measurement. Loris Riccardo Lopetuso received the Research Fellowship Award from the Crohn’s and Colitis Foundation of America (CCFA – CON125252). Franco Scaldaferri received a research prize and an ECCO grant from the Italian Society of Gastroenterology (SIGE). Alfredo Papa and Antonio Gasbarrini received research support from the Catholic University (Linea D1).
Received: 14.03.16 Accepted: 17.08.16
Citation: EMJ Gastroenterol. 2016;5[1]:107-115.

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.

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