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Poster presentations: Clinical: Therapy and Observation 2020

P630 Complete endoscopic remission is not only associated with higher mucosal concentrations of 5-aminosalicylic acid but also with N-acetyl-5-aminosalicylic acid in patients with ulcerative colitis

T. Fukuda1, M. Naganuma1, K. Takabayashi2, Y. Hagihara1, S. Tanemoto1, E. Nomura1, Y. Yoshimatsu1, S. Sugimoto1, K. Nanki1, S. Mizuno1, Y. Mikami1, K. Fukuhara3, T. Suzino1, M. Mutaguchi2, N. Inoue3, H. Ogata2, Y. Iwao3, T. Kanai1

1Keio University School of Medicine, Division of Gastroenterology and Hepatology- Department of Internal Medicine, Tokyo, Japan, 2Keio University School of Medicine, Center for Diagnostic and Therapeutic Endoscopy-, Tokyo, Japan, 3Keio University School of Medicine, Center for Preventive Medicine- Keio University School of Medicine-, Tokyo, Japan

Background

The mechanisms behind 5-aminosalicylic acid (5-ASA) activity in ulcerative colitis (UC) are known to exert a beneficial effect by acting topically on colonic mucosa. this study investigated whether mucosal 5-ASA and N-acetyl-5-ASA (Ac-5-ASA) concentrations are associated with endoscopic remission.

Methods

This single-centre, prospective cross-sectional study was conducted between March 2018 and February 2019. Patients with UC who were treated with 5-ASA medications for at least 8 weeks prior to sigmoidoscopy were enrolled. All participants underwent sigmoidoscopy without pre-treatment, and biopsies were performed to extract approximately 10 mg of tissue from the sigmoid colon and rectum. Mucosal concentrations of 5-ASA and Ac-5-ASA were measured using liquid chromatography with tandem mass spectrometry. The main endpoint was defined as the difference in mucosal concentrations of 5-ASA and Ac-5-ASA according to the level of either the Mayo endoscopic subscore (MES) or the ulcerative colitis Endoscopic Index of Severity (UCEIS).

Results

Mucosal concentrations were analysed in 50 patients. In the sigmoid colon, the median 5-ASA concentration in patients with MES of 0 (17.3 ng/mg) was significantly higher than MES ≥1 (6.4 ng/mg) (p = 0.019). The median 5-ASA concentration in patients with UCEIS ≤1 (16.4 ng/mg) was also significantly higher than in patients with UCEIS ≥2 (4.63 ng/mg) (p = 0.047). Interestingly, the concentration of Ac-5-ASA was higher in patients with an MES of 0 (21.2 ng/mg) than in patients with an MES≥1 (5.81 ng/mg) (p = 0.022). Similarly, the Ac-5-ASA concentration was significantly higher in patients with a UCEIS≤1 (21.1 ng/mg) compared with that in patients with a UCEIS≥2 (7.8 ng/mg) (p = 0.048). Furthermore, we compared the concentrations of 5-ASA in patients receiving the maximum dose of the three different formulations (time-dependent, pH-dependent, or multimatrix system 5-ASA). 5-ASA concentrations in both sigmoid colon and the rectum tended to be lower in patients receiving time-dependent 5-ASA than patients receiving pH-dependent 5-ASA or multimatrix system 5-ASA, but the difference was not significant.

Conclusion

Although Ac-5ASA, a metabolite of 5-ASA is thought to have few pharmacological effect, this study demonstrated that patients with complete endoscopic remission had higher mucosal concentrations of not only 5-ASA but also Ac-5-ASA than patients with mild-to-moderate endoscopic severity. This result may be explained by the fact that Ac-5-ASA remains as a metabolite of 5-ASA after contributing to the suppression of inflammation in patients with endoscopic remission.