Intest Res.  2020 Jan;18(1):69-78. 10.5217/ir.2019.00084.

5-Aminosalicylic acid intolerance is associated with a risk of adverse clinical outcomes and dysbiosis in patients with ulcerative colitis

• Mizuno S
• Ono K
• Mikami Y
• Naganuma M
• Fukuda T
• Minami K
• Masaoka T
• Terada S
• Yoshida T
• Saigusa K
• Hirahara N
• Miyata H
• Suda W
• Hattori M
• Kanai T

• KMID: 2501368
• DOI: http://doi.org/10.5217/ir.2019.00084

Abstract

Background/Aims
5-Aminosalicylic acid (ASA) causes intolerance reactions in some patients. This study was performed to examine the prognosis of patients with ulcerative colitis (UC) and 5-ASA intolerance, and to evaluate the potential interaction between 5-ASA intolerance and the intestinal microbiota.
Methods
We performed a retrospective cohort study of patients with UC who visited participating hospitals. The primary endpoint was to compare the incidence of hospitalization within 12 months between the 5-ASA intolerance group and the 5-ASA tolerance group. The secondary endpoint was to compare the risk of adverse clinical outcomes after the start of biologics between the 2 groups. We also assessed the correlation between 5-ASA intolerance and microbial change in an independently recruited cohort of patients with UC.
Results
Of 793 patients, 59 (7.4%) were assigned to the 5-ASA intolerance group and 734 (92.5%) were assigned to the 5-ASA tolerance group. The admission rate and incidence of corticosteroid use were significantly higher in the intolerance than tolerance group (P< 0.001). In 108 patients undergoing treatment with anti-tumor necrosis factor biologics, 5-ASA intolerance increased the incidence of additional induction therapy after starting biologics (P< 0.001). The 5-ASA intolerance group had a greater abundance of bacteria in the genera Faecalibacterium, Streptococcus, and Clostridium than the 5-ASA tolerance group (P< 0.05).
Conclusions
In patients with UC, 5-ASA intolerance is associated with a risk of adverse clinical outcomes and dysbiosis. Bacterial therapeutic optimization of 5-ASA administration may be important for improving the prognosis of patients with UC.

Keyword

5-Aminosalicylic acid; Colitis, ulcerative; Prognosis; Dysbiosis

Figure

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  Fig. 1. Flowchart of participants in the risk analysis for admission divided into the 5-aminosalicylic acid (5-ASA) tolerance group and the 5-ASA intolerance group.

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  Fig. 2. Risk analysis of 5-aminosalicylic acid (5-ASA) intolerance group compared with 5-ASA tolerance group. (A) Comparison of admission rate. (B) Forest plot of univariate analysis of drug-use risk. (C) Comparison of corticosteroid use. (D) Comparison of calcineurin inhibitor use. IM, immunomodulator.

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  Fig. 3. Proportion of patients with UC requiring induction therapy. (A) Kaplan–Meier curve of patients with or without immunomodulator (IM) use. (B) Kaplan–Meier curve of 5-aminosalicylic acid (5-ASA)-intolerant patients and 5-ASA-tolerant patients.

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  Fig. 4. Flowchart of participants in the microbial analysis. 5-ASA, 5-aminosalicylic acid.

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  Fig. 5. Analysis of the microbiome. (A, B) Microbiota diversity (OTU number) of 5-ASA-tolerant patients (n=112) and 5-ASA-intolerant patients (n=12). (C, D) Comparison of 5 fecal bacteria at the phylum level. (E, F) Comparison of the top 6 fecal bacteria at the genus level. 5-ASA, 5-aminosalicylic acid; OTU, operational taxonomic unit.

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