P021 Higher TNFα and IL-6 mucosal levels in ulcerative colitis patients with more severe endoscopic activity

Abstract

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterised by colonic mucosa inflammation. Its clinical course is marked by alternating periods of relapse and remission that impair patients' quality of life. In the last decades, novel therapies have shown to be effective for UC resulting in lower rates of colectomy. However, there is still a significant proportion of non-responding patients that change from one treatment to another, being exposed to its potential adverse events. Thus, predictive factors of response to available drugs are needed to tailor the best treatment strategy for each patient. The aim of our study was to measure TNFα and IL-6 levels in colonic biopsies from patients with UC with moderate to severe endoscopic activity. Methods A prospective, observational single-centre study was designed and it is currently on going. Adult UC patients with moderate to severe endoscopic activity (Mayo Endoscopic Score (MES) > 1) in a routine colonoscopy were included. Biopsies from inflamed (MES>1) and non-inflamed (MES=0) colon of each patient were homogenised and processed by using RIPA buffer and ultrasounds to obtain cell lysates. Human Luminex Discovery Assay (2 plex) was used for the simultaneous detection and quantitation of IL-6 and TNFα. Data are shown as percentage, median, interquartile range (IQR) and mean ± standard deviation (SD) as appropriate. Results So far, 21 patients were consecutively included (mean age 53.8 years (SD 17.0), 52.4% female). About 43% of patients had left-sided UC, 28.5% extensive UC and 28.5% proctitis. Regarding endoscopic activity, 61.9% of patients showed MES=2 and 38.1% were MES=3. Fourteen patients (66.6%) were bio-naïve and 7 (33.3%) had been exposed to anti-TNFα. IL-6 was detected in biopsies from colon with MES ≥ 2 of 18 (85.7%) patients, of which 10 (55.6%) patients also TNFα was found. Neither IL-6 nor TNFα were detected in biopsies from non-inflamed colon (p=0.00). Median IL-6 in inflamed colonic samples from patients with MES-2 was 25.6pg/ml (IQR 0.2-74.3) and 92.2pg/ml (IQR 16.9-314.3) in those with MES-3 (p=0.09). Median TNFα in inflamed colonic biopsies from patients with MES-2 was 0.0pg/ml (IQR 0.0-20.0) and 22.2pg/ml (IQR 0.0-34.3) in patients with MES-3 (p=0.12) (Figure 1). No differences were found in TNFα levels between anti-TNFα naïve patients and those patients previously exposed to anti-TNFα (p=0.96). Conclusion IL-6 and TNFα are elevated in inflamed colonic mucosa, particularly in those patients with more severe endoscopic activity, while they are not found in non-inflamed colonic mucosa. The correlation between cytokine levels and endoscopic severity suggests their potential as biomarkers for treatment response.