Background: The clinical course of ulcerative colitis (UC) is still unpredictable. There is no prognostic tool to foresee the future disease course at diagnosis, during or after medical treatments. We aimed to assess whether mucosal TNF-alpha levels (m-TNF-α) are able to predict sustained remission after the achievement of mucosal healing and to detect a threshold level for inflammation compared to endoscopic disease activity. Methods: Patients with Ulcerative Colitis who underwent endoscopic evaluation were included and samples were collected from June 2019 to June 2021. We collected also data from a control cohort with expected absence of colonic inflammation. Demographic, disease-and treatment-related data were collected from each patient. Expression of m- TNF-α levels was quantified by real-time PCR in mucosal biopsies. Primary outcome: to correlate m-TNF-α to treatment response with anti-TNF-alpha and, in patients with mucosal healing, to maintenance of remission. Secondary outcomes: to correlate m- TNF-α to clinical and endoscopic inflammation and to find a threshold level for detecting inflammation in tissue biopsies. Results: Forty patients with ulcerative colitis and 15 normal controls were included (UC: male 50%; mean age 44 ± 14.6 years; controls: male 53%; mean age 53 ± 12.9 years). Patients with UC had significantly higher m-TNF-α levels than controls (3373 copies/µg ± 4362 vs 1593 copies/µg ± 956; p= 0.033) and those with active UC had a significantly higher m-TNF-α concentration compared to those with mucosal healing and controls (p= 0.006). M-TNF-α correlated significantly also with the endoscopic Mayo score (p=0.007, rs=0.3) but not to the clinical partial Mayo score. The maintenance of remission during follow-up correlated with lower m-TNF-α levels (p=0.026). According to a threshold of 2084 copies/µg, m-TNF-α achieved for detecting inflammation a sensitivity of 47.5% (95%CI: 31.50 – 63.87%) and a specificity of 100% (95%CI: 78,20 – 100,00%) and an overall diagnostic accuracy of 61.82% (95%CI: 47.73 - 54.79%). The AUROC value was 0.688 (95% CI: 0.551-0.826; p=0.033). The threshold of 2084 copies/µg of m-TNF-α achieved a positive predictive value (PPV) of 100%. Conclusions Levels of m-TNFα were increased in UC patients with active disease compared to normal controls and patients in remission. Furthermore, in patients with inactive disease, lower m-TNF-α values were associated with maintenance of remission over the following 6 months. These results suggested a possible use of this biomarker in predicting treatment response.

Tissue levels of Tumour Necrosis Factor-alpha as molecular biomarker of inflammation and prediction of sustained treatment response in patients with Ulcerative Colitis.

VIOLA, Anna
2022-02-23

Abstract

Background: The clinical course of ulcerative colitis (UC) is still unpredictable. There is no prognostic tool to foresee the future disease course at diagnosis, during or after medical treatments. We aimed to assess whether mucosal TNF-alpha levels (m-TNF-α) are able to predict sustained remission after the achievement of mucosal healing and to detect a threshold level for inflammation compared to endoscopic disease activity. Methods: Patients with Ulcerative Colitis who underwent endoscopic evaluation were included and samples were collected from June 2019 to June 2021. We collected also data from a control cohort with expected absence of colonic inflammation. Demographic, disease-and treatment-related data were collected from each patient. Expression of m- TNF-α levels was quantified by real-time PCR in mucosal biopsies. Primary outcome: to correlate m-TNF-α to treatment response with anti-TNF-alpha and, in patients with mucosal healing, to maintenance of remission. Secondary outcomes: to correlate m- TNF-α to clinical and endoscopic inflammation and to find a threshold level for detecting inflammation in tissue biopsies. Results: Forty patients with ulcerative colitis and 15 normal controls were included (UC: male 50%; mean age 44 ± 14.6 years; controls: male 53%; mean age 53 ± 12.9 years). Patients with UC had significantly higher m-TNF-α levels than controls (3373 copies/µg ± 4362 vs 1593 copies/µg ± 956; p= 0.033) and those with active UC had a significantly higher m-TNF-α concentration compared to those with mucosal healing and controls (p= 0.006). M-TNF-α correlated significantly also with the endoscopic Mayo score (p=0.007, rs=0.3) but not to the clinical partial Mayo score. The maintenance of remission during follow-up correlated with lower m-TNF-α levels (p=0.026). According to a threshold of 2084 copies/µg, m-TNF-α achieved for detecting inflammation a sensitivity of 47.5% (95%CI: 31.50 – 63.87%) and a specificity of 100% (95%CI: 78,20 – 100,00%) and an overall diagnostic accuracy of 61.82% (95%CI: 47.73 - 54.79%). The AUROC value was 0.688 (95% CI: 0.551-0.826; p=0.033). The threshold of 2084 copies/µg of m-TNF-α achieved a positive predictive value (PPV) of 100%. Conclusions Levels of m-TNFα were increased in UC patients with active disease compared to normal controls and patients in remission. Furthermore, in patients with inactive disease, lower m-TNF-α values were associated with maintenance of remission over the following 6 months. These results suggested a possible use of this biomarker in predicting treatment response.
23-feb-2022
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3222860
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