Mucosal concentrations of N-acetyl-5-aminosalicylic acid related to endoscopic activity in ulcerative colitis patients with mesalamine

J Gastroenterol Hepatol. 2020 Nov;35(11):1878-1885. doi: 10.1111/jgh.15059. Epub 2020 Apr 20.

Abstract

Background and aim: 5-Aminosalicylic acid (5-ASA) is a fundamental treatment for mild-to-moderate ulcerative colitis (UC). 5-ASA is taken up into the colonic mucosa and metabolized to N-acetyl-5-ASA (Ac-5-ASA). Few studies have assessed whether mucosal 5-ASA and Ac-5-ASA concentrations are associated with endoscopic remission. This study aimed to investigate differences in 5-ASA and Ac-5-ASA concentrations according to endoscopic activity.

Methods: This single-center, prospective, cross-sectional study was conducted between March 2018 and February 2019. UC patients who were administered with 5-ASA medication for at least 8 weeks before sigmoidoscopy were enrolled. Mucosal 5-ASA and Ac-5-ASA concentrations were measured using liquid chromatography with tandem mass spectrometry. The primary endpoint was defined as the difference in mucosal concentrations of 5-ASA and Ac-5-ASA, according to the Mayo endoscopic subscore (MES).

Results: Mucosal concentrations were analyzed 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 concentrations in patients with Ulcerative Colitis Endoscopic Index of Severity ≤ 1 (16.4 ng/mg) were also significantly higher than in patients with Ulcerative Colitis Endoscopic Index of Severity ≥ 2 (4.63 ng/mg) (P = 0.047). In the sigmoid colon, the concentration of Ac-5-ASA was higher in patients with MES of 0 (21.2 ng/mg) than in patients with MES ≥ 1 (5.81 ng/mg) (P = 0.022).

Conclusions: The present study showed that mucosal Ac-5-ASA concentrations, as well as 5-ASA concentrations, are higher in UC patients with endoscopic remission. Ac-5-ASA may be useful for a biomarker of 5-ASA efficacy.

Keywords: 5-Aminosalicylic acid; Mucosal concentration; Ulcerative colitis.

MeSH terms

  • Adult
  • Aminosalicylic Acids / metabolism*
  • Biomarkers / metabolism
  • Colitis, Ulcerative / diagnosis
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / metabolism
  • Colon, Sigmoid / metabolism
  • Cross-Sectional Studies
  • Female
  • Humans
  • Intestinal Mucosa / metabolism*
  • Male
  • Mesalamine / metabolism
  • Mesalamine / therapeutic use*
  • Middle Aged
  • Prospective Studies
  • Remission Induction
  • Sigmoidoscopy*
  • Treatment Outcome

Substances

  • Aminosalicylic Acids
  • Biomarkers
  • Mesalamine
  • N-acetyl-5-aminosalicylic acid