P494 Monocytic TNF production predicts response to infliximab treatment in Crohn’s disease but not ulcerative colitis

Abstract

One third of all patients with inflammatory bowel diseases (IBD) do not respond to initial treatment with the TNF-antibody Infliximab. Thus, predictive markers for response to anti-TNF-treatment are required. The study’s aim was to investigate whether levels of TNF produced by peripheral blood mononuclear cells (PBMCs) are associated with response to anti-TNF-treatment. Thirty-one patients with proven Crohn’s disease (CD) or ulcerative colitis (UC) without treatment with biologicals in the past 6 months were included prior to first infliximab treatment. Disease activity was measured by the use of Harvey–Bradshaw Index (HBI) or partial Mayo score, C-reactive protein (CRP) and ultrasound (Limberg score). TNF-expression of LPS-stimulated PBMCs was measured by ELISA before treatment in CD and UC patients and 11 healthy controls. Additionally, intracellular TNF expression of PBMCs was analysed by flow cytometry. According to a cut-off of 400 pg/ml, patients were divided into low- and high-TNF producers. Primary endpoint was clinical response, secondary endpoints were remission, laboratory values and ultrasound findings. Clinical response was defined as a decline in score of ≥ 2 (HBI) or ≥ 3 (partial Mayo score). An HBI of <5 or a partial Mayo score of <2 was defined as remission. Results were analysed using Fisher’s exact test. Twenty-one patients reached the endpoint at Week 6 and were available for further analysis (11 patients with CD, 10 patients with UC). The mean TNF-production was 714, .01 pg/ml (50–1500 pg/ml). Levels were higher in CD than in UC patients (810 vs. 608 pg/ml) and healthy controls (455 pg/ml). In all groups, TNF was mainly produced by CD14+ monocytes. Seven patients were identified as low producers (2 CD, 5 UC) and 14 as high producers (9 CD, 5 UC). High producers rather responded to treatment regarding clinical scoring (high: 93% vs. low: 43% clinical response, p = 0.025). Subgroup analysis revealed that all high producers with CD responded to Infliximab, whereas none of the low producers did (high: 100% vs. low: 0% clinical response in CD, p = 0.018), which was not true for UC patients (high 80% vs. low 60% clinical response, not significant). Similar tendencies could be seen for clinical remission though not significant. Quantification of TNF-expression in PBMCs and the resulting classification in low- and high-producers could be a potential predictive marker for response to anti-TNF-treatment especially in Crohn’s disease patients.