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. 2019 Mar;53(3):210-215.
doi: 10.1097/MCG.0000000000001002.

Inflammatory Cytokine Profile in Crohn's Disease Nonresponders to Optimal Antitumor Necrosis Factor Therapy

Andres J Yarur  1 , Anjali Jain  2 , Maria A Quintero  3 , Frank Czul  3 , Amar R Deshpande  3 , David H Kerman  3 , Maria T Abreu  3
Affiliations

Inflammatory Cytokine Profile in Crohn's Disease Nonresponders to Optimal Antitumor Necrosis Factor Therapy

Andres J Yarur et al. J Clin Gastroenterol. 2019 Mar.

Abstract

Background: A significant number of patients receiving therapy with antitumor necrosis factor (TNF) agents for Crohn's disease experience primary or secondary nonresponse. The aim of this study was to assess whether patients with nonresponse to anti-TNF agents have increased expression of alternative cytokine pathways.

Methods: We designed a prospective, cross-sectional study that included patients with Crohn's disease receiving anti-TNF undergoing colonoscopy with adequate serum trough drug levels (≥8 µg/mL) and without anti-drug antibodies. Inflammatory cytokines and cell adhesions markers measured included intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1, interleukin (IL)-8, IL-1β, and IL-6. The primary outcome was the presence of active endoscopic inflammation defined as the presence of at least 1 ulceration ≥5 mm.

Results: In total, 47 patients were included. Patients with active inflammation had significantly higher levels of ICAM-1 and IL-1β when compared with those without intestinal inflammation (45.9 vs. 35.8 ng/mL, P<0.0001 and 3.2 vs. 1.5 pg/mL, P=0.002, respectively). There were no significant differences in the other study variables. Using receiving operating curves, ICAM and IL-1β had a good correlation (receiver operating characteristic ≥0.8) with inflammation in this cohort of patients with "anti-TNF resistance." The results were similar in the group of patients with previous anti-TNF exposure.

Conclusion: Our study suggests that patients who have active inflammation with seemingly adequate serum anti-TNF levels have increased levels of specific inflammatory pathways that may serve as biomarkers of nonresponse as well as potential targets of therapy in anti-TNF nonresponders.

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Conflict of interest statement

Conflicts of Interest

Andres J. Yarur, MD: consultant and part of the speaker bureau for Prometheus Laboratories.

Anjali Jain, PhD: employee of Prometheus Laboratories.

Maria A Quintero, MD: no conflicts of interest

Frank Czul, MD: no conflicts of interest

Amar R. Deshpande, MD: no conflicts of interest

David H. Kerman, MD: no conflicts of interest

Maria T. Abreu, MD: conception and design of the study, analysis and interpretation of data, and final approval of the submitted version submitted.

Figures

Figure 1
Figure 1
Differences in serum soluble adhesion molecule levels between those patients with and without active endoscopic inflammation despite adequate drug levels. (*) are statistically significant
Figure 2
Figure 2
Differences in serum cytokine levels between those patients with and without active endoscopic inflammation despite adequate drug levels. (*) are statistically significant
Figure 3
Figure 3
Area under the curve showing the correlation between active endoscopic disease and ICAM-1 (Figure 3A) and IL-1β (Figure 3B)
See this image and copyright information in PMC

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