5-aminosalicylate–intolerant patients are at increased risk of colectomy for ulcerative colitis
Shuji Hibiya
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorYusuke Matsuyama
Department of Global Health Promotion, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Toshimitsu Fujii
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Correspondence
Toshimitsu Fujii, Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Email: [email protected]
Search for more papers by this authorChiaki Maeyashiki
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
Search for more papers by this authorEiko Saito
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorKimiko Ito
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorHiromichi Shimizu
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorAmi Kawamoto
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorMaiko Motobayashi
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorKento Takenaka
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Endoscopic Unit, Tokyo Medical and Dental University Hospital, Tokyo, Japan
Search for more papers by this authorMasakazu Nagahori
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorMasayuki Kurosaki
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
Search for more papers by this authorTsunehito Yauchi
Department of Gastroenterology, Soka Municipal Hospital, Saitama, Japan
Search for more papers by this authorKazuo Ohtsuka
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Endoscopic Unit, Tokyo Medical and Dental University Hospital, Tokyo, Japan
Search for more papers by this authorTakeo Fujiwara
Department of Global Health Promotion, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorRyuichi Okamoto
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorMamoru Watanabe
TMDU Advanced Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorShuji Hibiya
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorYusuke Matsuyama
Department of Global Health Promotion, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Toshimitsu Fujii
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Correspondence
Toshimitsu Fujii, Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Email: [email protected]
Search for more papers by this authorChiaki Maeyashiki
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
Search for more papers by this authorEiko Saito
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorKimiko Ito
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorHiromichi Shimizu
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorAmi Kawamoto
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorMaiko Motobayashi
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorKento Takenaka
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Endoscopic Unit, Tokyo Medical and Dental University Hospital, Tokyo, Japan
Search for more papers by this authorMasakazu Nagahori
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorMasayuki Kurosaki
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
Search for more papers by this authorTsunehito Yauchi
Department of Gastroenterology, Soka Municipal Hospital, Saitama, Japan
Search for more papers by this authorKazuo Ohtsuka
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Endoscopic Unit, Tokyo Medical and Dental University Hospital, Tokyo, Japan
Search for more papers by this authorTakeo Fujiwara
Department of Global Health Promotion, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorRyuichi Okamoto
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorMamoru Watanabe
TMDU Advanced Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorSummary
Background
Although 5-aminosalicylate (5-ASA) is the therapy of first choice in ulcerative colitis (UC), some patients cannot tolerate it because of side effects. Previous reports have not investigated whether 5-ASA intolerance is associated with the risk of colectomy.
Aim
To investigate the associations between 5-ASA tolerance and colectomy among UC patients
Methods
The data of UC patients who visited any of three hospitals during 2014-2018 in and around Tokyo, Japan, were retrospectively obtained from the medical records. Patients were categorized as (a) tolerant to any 5-ASA compounds (“tolerant to 5-ASA”) and (b) patients who were intolerant to one or more 5-ASA compounds leading to refrainment from their further use (“intolerant to 5-ASA”). The association between 5-ASA tolerance and colectomy was examined by Cox proportional hazards model adjusted for sex, age, smoking and extent of colitis.
Results
Of 1788 patients, 1684 were “tolerant to 5-ASA” while 104 were “intolerant to 5-ASA”. Colectomy was performed in 43 (2.6%) of the patients tolerant to 5-ASA and 12 (11.5%) of the patients intolerant to 5-ASA. After adjusting for all covariates, the risk of undergoing colectomy was higher in the “intolerant to 5-ASA” group than in the “tolerant to 5-ASA” group (hazard ratio: 4.92; 95% confidence interval: 2.58-9.38).
Conclusion
Patients in whom 5-ASA was discontinued due to intolerance had a higher risk of undergoing colectomy than patients tolerant to their first, second or third 5-ASA compounds.
Supporting Information
| Filename | Description |
|---|---|
| apt16120-sup-0001-TableS1.docxWord document, 17.2 KB | Table S1 |
| apt16120-sup-0002-TableS2.docxWord document, 17.2 KB | Table S2 |
| apt16120-sup-0003-TableS3.docxWord document, 17.1 KB | Table S3 |
| apt16120-sup-0004-TableS4.docxWord document, 18.4 KB | Table S4 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Rutter M, Saunders B, Wilkinson K, et al. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology. 2004; 126: 451-459.
- 2Harbord M, Eliakim R, Bettenworth D, et al. Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 2: current management. J Crohns Colitis. 2017; 11: 769-784.
- 3Desreumaux P, Ghosh S. Review article: mode of action and delivery of 5-aminosalicylic acid – new evidence. Aliment Pharmacol Ther. 2006; 24: 2-9.
- 4Ford AC, Achkar J-P, Khan KJ, et al. Efficacy of 5-aminosalicylates in ulcerative colitis: systematic review and meta-analysis. Am J Gastroenterol. 2011; 106: 601-616.
- 5Ransford RAJ, Langman MJS. Sulphasalazine and mesalazine: serious adverse reactions re-evaluated on the basis of suspected adverse reaction reports to the Committee on Safety of Medicines. Gut. 2002; 51: 536-539.
- 6Chakraborty TK, Bhatia D, Heading RC, Ford MJ. Salicylate induced exacerbation of ulcerative colitis. Gut. 1987; 28: 613-615.
- 7Sturgeon JB, Bhatia P, Hermens D, Miner PB. Exacerbation of chronic ulcerative colitis with mesalamine. Gastroenterology. 1995; 108: 1889-1893.
- 8Kapur KC, Williams GT, Allison MC. Mesalazine induced exacerbation of ulcerative colitis. Gut. 1995; 37: 838-839.
- 9Di Paolo MC, Paoluzi OA, Pica R, et al. Sulphasalazine and 5-aminosalicylic acid in long-term treatment of ulcerative colitis: report on tolerance and side-effects. Dig Liver Dis. 2001; 33: 563-569.
- 10Mizuno S, Ono K, Mikami Y, et al. 5-Aminosalicylic acid intolerance is associated with a risk of adverse clinical outcomes and dysbiosis in patients with ulcerative colitis. Intest Res. 2020; 18: 69-78.
- 11Chhaya V, Saxena S, Cecil E, et al. The impact of timing and duration of thiopurine treatment on colectomy in ulcerative colitis: a national population-based study of incident cases between 1989–2009. Aliment Pharmacol Ther. 2015; 41: 87-98.
- 12Al-Darmaki A, Hubbard J, Seow CH, et al. Clinical predictors of the risk of early colectomy in ulcerative colitis: a population-based study. Inflamm Bowel Dis. 2017; 23: 1272-1277.
- 13Giaffer MH, O’Brien CJ, Holdsworth CD. Clinical tolerance to three 5-aminosalicylic acid releasing preparations in patients with inflammatory bowel disease intolerant or allergic to sulphasalazine. Aliment Pharmacol Ther. 1992; 6: 51-59.
- 14Xie C, Quan R, Hong F, Zou K, Yan W, Fu Y. The culprit of mesalamine intolerance: case series and literature review. BMC Gastroenterol. 2019; 19: 138.
- 15 Japan Intractable Diseases Information Center. https://www.nanbyou.or.jp/entry/62. Accessed September 26, 2020.
- 16Fumery M, Singh S, Dulai PS, Gower-Rousseau C, Peyrin-Biroulet L, Sandborn WJ. Natural history of adult ulcerative colitis in population-based cohorts: a systematic review. Clin Gastroenterol Hepatol. 2018; 16: 343–356.e3.
- 17Shi HY, Chan FKL, Leung WK, et al. Natural history of elderly-onset ulcerative colitis: results from a territory-wide inflammatory bowel disease registry. J Crohns Colitis. 2016; 10: 176-185.
- 18D’Haens G, Sandborn WJ, Barrett K, Hodgson I, Streck P. Once-daily MMX(®) mesalamine for endoscopic maintenance of remission of ulcerative colitis. Am J Gastroenterol. 2012; 107: 1064-1077.
- 19Kamm MA, Sandborn WJ, Gassull M, et al. Once-daily, high-concentration mmx mesalamine in active ulcerative colitis. Gastroenterology. 2007; 132: 66-75.
- 20Ito H, Iida M, Matsumoto T, et al. Direct comparison of two different mesalamine formulations for the induction of remission in patients with ulcerative colitis: a double-blind, randomized study. Inflamm Bowel Dis. 2010; 16: 1567-1574.
- 21Prantera C, Kohn A, Campieri M, et al. Clinical trial: ulcerative colitis maintenance treatment with 5-ASA: a 1-year, randomized multicentre study comparing MMX® with Asacol®. Aliment Pharmacol Ther. 2009; 30: 908-918.
- 22Kawashima K, Ishihara S, Yuki T, et al. Therapeutic efficacy of pH-dependent release formulation of mesalazine on active ulcerative colitis resistant to time-dependent release formulation: analysis of fecal calprotectin concentration. BioMed Res Int. 2014; 2014: 1-6.
- 23Feagan BG, Chande N, MacDonald JK. Are there any differences in the efficacy and safety of different formulations of Oral 5-ASA used for induction and maintenance of remission in ulcerative colitis? Evidence from cochrane reviews. Inflamm Bowel Dis. 2013; 19: 2031-2040.
- 24Yasutomi E, Hiraoka S, Yamamoto S, et al. Switching between three types of mesalazine formulation and sulfasalazine in patients with active ulcerative colitis who have already received high-dose treatment with these agents. J Clin Med. 2019; 8: 2109.
- 25Travis SP, Farrant JM, Ricketts C, et al. Predicting outcome in severe ulcerative colitis. Gut. 1996; 38: 905-910.
- 26Bojic D, Radojicic Z, Nedeljkovic-Protic M, Al-Ali M, Jewell DP, Travis SPL. Long-term outcome after admission for acute severe ulcerative colitis in Oxford: the 1992–1993 cohort. Inflamm Bowel Dis. 2009; 15: 823-828.
- 27Kles KA, Vavricka SR, Turner JR, Musch MW, Hanauer SB, Chang EB. Comparative analysis of the in vitro prosecretory effects of balsalazide, sulfasalazine, olsalazine, and mesalamine in rabbit distal ileum. Inflamm Bowel Dis. 2005; 11: 253-257.
- 28Gonzalo MA, Alcalde MM, García JM, Alvarado MI, Fernández L. Desensitization after fever induced by mesalazine. Allergy. 1999; 54: 1224-1225.
- 29Slim R, Amara J, Nasnas R, et al. Isolated fever induced by mesalamine treatment. World J Gastroenterol. 2013; 19: 1147-1149.
- 30Lim AG, Hine KR. Fever, vasculitic rash, arthritis, pericarditis, and pericardial effusion after mesalazine. BMJ. 1994; 308: 113.
- 31Kaiser GC, Milov DE, Erhart NA, Bailey DJ. Massive pericardial effusion in a child following the administration of mesalamine. J Pediatr Gastroenterol Nutr. 1997; 25: 435-438.
- 32Foster RA, Zander DS, Mergo PJ, Valentine JF. Mesalamine-related lung disease: clinical, radiographic, and pathologic manifestations. Inflamm Bowel Dis. 2003; 9: 308-315.
- 33Sviri S, Gafanovich I, Kramer MR, Tsvang E, Ben-Chetrit E. Mesalamine-induced hypersensitivity pneumonitis: a case report and review of the literature. J Clin Gastroenterol. 1997; 24: 34-36.
- 34Hoie O, Wolters FL, Riis L, et al. Low colectomy rates in ulcerative colitis in an unselected European cohort followed for 10 years. Gastroenterology. 2007; 132: 507-515.
- 35Parragi L, Fournier N, Zeitz J, et al. Colectomy rates in ulcerative colitis are low and decreasing: 10-year follow-up data from the Swiss IBD cohort study. J Crohns Colitis. 2018; 12: 811-818.
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