P780 Prognosis and optimal treatment for 5-aminosalicylic acid-intolerant patients with Ulcerative Colitis

• Published in: Journal of Crohn's and colitis Vol. 17; no. Supplement_1; pp. i913 - i914
• Main Authors: Yaguchi, K, Kinoshita, H, Kunisaki, R, Madarame, A, Tatsuno, M, Nishikawa, Y, Hama, T, Onishi, M, Kobayashi, K, Shibui, S, Toritani, K, Nishida, D, Matsubayashi, M, Nakamori, Y, Nishio, M, Umezawa, S, Ogashiwa, T, Sasaki, T, Fujii, A, Kimura, H, Kato, J, Maeda, S
• Format: Journal Article
• Language: English
• Published: 30-01-2023
• ISSN: 1873-9946; 1876-4479
• DOI: 10.1093/ecco-jcc/jjac190.0910

Abstract
Background
5-aminosalicylic acid (5-ASA) is widely used as a first-line treatment for ulcerative colitis (UC), but intolerance sometimes occurs. 5-ASA-intolerance was considered a risk factor for colectomy in UC patients, but no reports have examined which treatment is suitable to avoid colectomy in 5-ASA-intolerant UC patients. This is the first report describing a treatment strategy for 5-ASA-intolerant UC. The aims of this study were to determine the optimal therapeutic strategy in 5-ASA-intolerant UC patients.
Methods
This retrospective cohort study involved patients who were newly diagnosed as having UC after January 2010 and who received oral 5-ASA agents. Patients were considered 5-ASA-intolerant when they fulfilled two or more of the following conditions: (1) paradoxical aggravation of colitis on introducing oral 5-ASA agents or allergic reactions to the agents; (2) obvious improvement of abdominal symptoms after discontinuation of 5-ASA agents; (3) positive drug-induced lymphocyte stimulation test (DLST) for at least two formulations of 5-ASA; (4) adverse events following re-challenge with 5-ASA agents; and (5) severe adverse events owing to 5-ASA agents.
Results
Of 950 UC patients with a history of 5-ASA administration, 213 (22.4%) were considered 5-ASA-intolerant. Five-year colectomy-free survival was significantly lower in 5-ASA-intolerant patients compared with 5-ASA-tolerant patients (73% vs. 84%, respectively). From the multivariate Cox proportional hazards model analysis in the 5-ASA-intolerant patient cohort, thiopurine use was shown to contribute to avoidance of colectomy in 5-ASA-intolerant patients (hazard ratio = 0.25; 95% confidence interval, 0.13–0.47; P < 0.001); however, 5-ASA-intolerant patients were also likely to be thiopurine-intolerant compared with 5-ASA-tolerant patients (27% vs. 15%, respectively; P = 0.04). Calcineurin inhibitor use was associated with an increased risk of colectomy (hazard ratio = 4.80; 95% confidence interval, 2.24–10.3; P < 0.001), while treatment with systemic corticosteroids and biologics did not affect the colectomy rate (hazard ratio = 1.07; 95% confidence interval, 0.60–1.91; P = 0.81).
Conclusion
Treatment with thiopurines demonstrated the potential to improve the prognosis in 5-ASA-intolerant patients. However, it should be noted that thiopurine intolerance was more frequent in 5-ASA-intolerant patients. Compared to biologics, calcineurin inhibitors may not contribute to avoidance of colectomy, and biologics may be preferred for intractable patients with 5-ASA intolerance. This is the first report describing a treatment strategy for 5-ASA-intolerant UC, and we believe it will have many implications in clinical practice.