5-aminosalicylate–Intolerant Patients Are at Increased Risk of Colectomy for Ulcerative Colitis

Shuji Hibiya; Yusuke Matsuyama; Toshimitsu Fujii; Chiaki Maeyashiki; Eiko Saito; Kimiko Ito; Hiromichi Shimizu; Ami Kawamoto; Maiko Motobayashi; Kento Takenaka; Masakazu Nagahori; Masayuki Kurosaki; Tsunehito Yauchi; Kazuo Ohtsuka; Takeo Fujiwara; Ryuichi Okamoto; Mamoru Watanabe

Disclosures

Aliment Pharmacol Ther. 2020;53(1):103-113. 

In This Article

Abstract and Introduction

Abstract

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.

Introduction

Ulcerative colitis (UC) is an incurable inflammatory bowel disease with unknown causes. Long-term management to induce and maintain clinical remission is important to prevent symptomatic relapse and minimize the risk for colorectal cancer and colectomy.[1] The first-choice therapy in both remission and maintenance in UC is 5-aminosalicylate (5-ASA).[2] 5-ASA acts topically in the colon to modulate anti-inflammatory and immunosuppressive properties,[3] and it is the key drug for treatment in UC because of the high efficiency for inducing and maintaining remission.[4] However, some patients are diagnosed as being 5-ASA intolerant after taking oral 5-ASA compounds. Serious adverse drug reactions can occur among them,[5] and several case reports have described exacerbation of UC in 5-ASA–intolerant patients.[6–8] Intolerance to 5-ASA occurs in ≤20% of UC patients.[5,9] However, studies focused on 5-ASA–intolerant patients have been limited. A previous study has reported that 5-ASA intolerance was associated with increased use of immunosuppressive agents and incidence of dysbiosis,[10] but the study did not mention whether 5-ASA intolerance affects chance of undergoing colectomy. A few studies have reported the effect of 5-ASA on the incidence of colectomy, although they did not report on 5-ASA intolerance,[11,12] and the findings are not consistent. Previous reports have not clarified whether 5-ASA intolerance affects the risk of undergoing colectomy, and to our knowledge, no study has reported on the impact on incidence of colectomy among 5-ASA–intolerant UC patients. Evaluating the prognosis of UC patients according to 5-ASA tolerance status would be valuable in a clinical setting. Further, some patients are tolerant to alternative 5-ASA compounds even if they are intolerant to the first compound tried.[13,14] Thus, describing the prognosis in relation to detailed 5-ASA tolerance (ie tolerant to first 5-ASA vs intolerant to first but tolerant to second or third 5-ASA) would also provide useful information for clinicians. In the present study, we aimed to investigate the association between 5-ASA tolerance and colectomy in UC patients.

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