No abstract

BACKGROUND: Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation. Tumor Necrosis Factor a (TNFa) levels have been found to be elevated in the intestinal mucosa of patients with Crohn's Disease (CD) and Ulcerative Colitis (UC), which turned the anti-TNFa agents as one of the mainstays of the treatment. Nevertheless, some patients fail to respond or loose response, despite adequate plasmatic levels of anti-TNFa agents. The aim of this study was to determine intestinal mucosa levels of infliximab (IFX) and TNFa and its possible association with their plasmatic levels and the endoscopic activity in IBD patients. METHODS: Cross–sectional study of patients with IBD enrolled at the IBD program of Clínica Las Condes, Chile. The enrollment was done between May 2016 and January 2017. Tissue and plasmatic IFX and TNFa samples were taken the same day just before the next IFX infusion. The endoscopic activity was determined by colonoscopy using Mayo Score for UC and SES-CD/Rutgeerts for CD. Samples of mucosa were taken from colon in patients in remission and from inflamed and non-inflamed colon tissue in active patients. Mucosal levels of IFX and TNFa were normalized by total protein levels. The statistical analysis was performed using paired t-test analysis for comparison between inflamed and non-inflamed sites and an alpha value of <0.05 was considered statistically significant. RESULTS: Fourteen patients were included (9 UC and 5 CD) of which 6 were in remission and 8 with active disease (2 mild, 5 moderate and 1 severe). Plasmatic levels of IFX were higher in patients in remission compared to patients with active disease (4.488 AU/mL vs 2.378 AU/mL; P = 0.1355). In this last group, higher levels were observed in patients with mild than moderate endoscopic activity (4.785 AU/mL vs 1.552 AU/mL; P = 0.0264). Plasmatic TNFa levels were higher in patients with active disease compared to patients in remission (111.938 pg/mL vs 23.467 pg/mL; P = 0.0011), as opposed to IFX levels. Mucosal IFX levels were higher in patients with active disease vs remission, not statistically significant (6.136 ng/mL vs 3.917 ng/mL; P = 0.1186). On the contrary, mucosal TNFa levels were significantly higher in patients in remission vs active disease (65.062 pg/mL vs 36.479 pg/mL; P = 0.0330). In patients with active disease (n = 8), there was no statistical difference between the IFX level in the inflamed compared to the non-inflamed mucosa (6.136 ng/mL vs 5.000 ng/mL; P = 0.3534). TNFa in the non-inflamed mucosa was significantly higher compared to inflamed mucosa (64.846 pg/mL vs 36.479 pg/mL; P = 0.0066). In both, no difference was observed according to endoscopic activity level. The proportion of IFX/TNFα in mucosa was higher in patients with mild and moderate activity (0.182 and 0.179, respectively) than patients with severe activity (0.074). CONCLUSION(S): The discordance between plasmatic and intestinal mucosa IFX and TNFα, in patients with active disease, indicate that the inflammatory cascade might be determined by others specific inflammatory pathways. Further studies need to be performed in a larger sample of patients to better elucidate the mechanistic explanation for persistent inflammation in certain IBD patients.