Oral 5-aminosalicylic acid for maintenance of surgically-induced remission in Crohn’s disease

Gordon M, Naidoo K, Thomas AG, Akobeng AK

Published Online:

August 10, 2011

Prevention of relapse is a key objective in the management of Crohn’s disease. There is no current treatment available that completely maintains remission and is without significant side-effects. 5-ASA (aminosalicylic acid) preparations have previously been shown to be ineffective in maintaining medically-induced remission of Crohn's disease. This review included nine studies. Seven studies compared 5-ASA drugs with placebo (inactive pills or tablets) and two studies compared 5-ASA drugs with antimetabolites (azathioprine or 6-mercaptopurine). The results of this review suggest that 5-ASA preparations may provide a modest benefit for maintaining surgically-induced remission of Crohn's disease. The results of the review should be interpreted with caution due to methodological and statistical issues in the included studies. 5-ASA drugs are safe for patients with Crohn's disease. Side effects were generally mild in nature and typically included nausea, vomiting, diarrhea, abdominal pain and dyspepsia (upset stomach or indigestion). There is insufficient evidence to allow any conclusions on how 5-ASA preparations compare with azathioprine or 6-mercaptopurine. In conclusion, there is some evidence that suggests 5-ASA preparations may provide a modest benefit for the maintenance of surgically-induced remission in patients with Crohn’s disease.

Abstract (click to read)

Background:

The use of 5-aminosalicylates (5-ASAs) in Crohn's disease (CD) is controversial. A recent Cochrane review found that 5-ASAs are not effective for the maintenance of medically-induced remission in CD, but their role in the maintenance of surgically-induced remission is unclear.

Objectives:

The objectives were to evaluate the efficacy and safety of 5-ASA agents for the maintenance of surgically-induced remission in CD.

Search strategy:

The search was standardised and not limited by language and included electronic searching (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Inflammatory Bowel Disease Group Specialized Trials Register), reference searching of all included studies, abstracts from major meetings, personal contacts and drug companies.

Selection criteria:

Randomised controlled trials (RCTs) which compared 5-ASAs with either placebo or another intervention, with treatment durations of at least 6 months were considered for inclusion. Participants were patients of any age with CD in remission following surgery. Primary outcome measures were clinical relapse or endoscopic recurrence as defined by the primary studies. Secondary endpoints were the occurrence of adverse events.

Data collection and analysis:

Relevant papers were identified and the authors independently assessed the eligibility of trials. Methodological quality was assessed using the Cochrane risk of bias tool.The Cochrane RevMan software was used for analyses. Patients with final missing outcomes were assumed to have relapsed. Odds ratio (OR) and 95% confidence intervals (95% CI) were calculated based on the fixed effects model. The chi square and I2 statistics were used to assess statistical heterogeneity.

Main results:

Nine RCTs were included in the review. Seven studies compared oral 5-ASA with placebo and two compared oral 5-ASA with purine antimetabolites (azathioprine or 6-mercaptopurine). 5-ASA was significantly more effective than placebo for preventing relapse (OR 0.68, 95% CI, 0.52 to 0.90). There was no statistically significant heterogeneity among the 8 trials comparing 5-ASA with placebo (P=0.47). No statistically significant difference in adverse events was found for 5-ASA versus placebo (OR 1.02, 95%CI, 0.60 to 1.76). No statistically significant difference was found between 5-ASA and purine antimetabolites for preventing relapses (OR 1.08 95% CI, 0.63 to 1.85).

Authors' conclusions:

The pooled analyses suggest that 5-ASA preparations may be superior to placebo for the maintenance of surgically-induced remission in patients with CD. The results of the pooled analyses should be interpreted with caution because adequately powered studies demonstrated no difference and publication bias (failure to publish negative studies) may be an issue. The potential benefit provided by 5-ASA drugs is modest with a number needed to treat of approximately 16 to 19 patients to avoid one relapse which raises issues about the cost-effectiveness of this therapy. However, 5-ASA drugs are safe and well tolerated. The incidence of adverse events was not different in patients receiving 5-ASA compared with those receiving placebo. There is insufficient evidence to allow any conclusions on how 5-ASA preparations compare with azathioprine or 6-mercaptopurine.

This record should be cited as:

Gordon M, Naidoo K, Thomas AG, Akobeng AK. Oral 5-aminosalicylic acid for maintenance of surgically-induced remission in Crohn's disease. Cochrane Database of Systematic Reviews 2011, Issue 1. Art. No.: CD008414. DOI: 10.1002/14651858.CD008414.pub2

Assessed as up to date:

May 10, 2010

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Primary Review Group:

Inflammatory Bowel Disease and Functional Bowel Disorders Group

Health topics:

Gastroenterology > Inflammatory bowel disease > Crohn's disease: maintenance of remission

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Oral 5-aminosalicylic acid for maintenance of surgically-induced remission in Crohn’s disease

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