5-ASA suppositories, enemas or foam for induction of remission in ulcerative colitis

Ulcerative colitis (UC) is a chronic condition wherein the innermost lining of the large bowel becomes inflamed. If UC affects only the last part of the bowel (distal UC), medications can be given rectally. 5-Aminosalicylic acid (5-ASA) is used commonly to treat mild to moderately active UC. A review of the literature was undertaken to determine how effective rectal 5-ASA (e.g. enemas, suppositories or foam) is for treating distal UC. Thirty-eight studies met the criteria for inclusion in the review. Pooled results from these studies show that rectal 5-ASA is superior to placebo (fake suppositories, enemas or foam) for improving symptoms, improving the appearance of the bowel lining at colonoscopy, and improving the appearance of biopsies of the bowel examined microscopically. Rectal 5-ASA is also superior to rectal steroids for improving symptoms. Side effects were generally mild in nature and included abdominal pain or distention, nausea and anal discomfort or irritation. From these results, it was concluded that rectal 5-ASA should be a first-line treatment for patients with mild to moderately active distal UC.

Authors' conclusions: 

Rectal 5-ASA should be considered a first-line therapy for patients with mild to moderately active distal UC. The optimal total daily dose and dose frequency of 5-ASA remain to be determined. Future research should define differences in efficacy among patient subgroups defined by proximal disease margin and disease activity. There is a strong need for consensus standardization of outcome measurements for clinical trials in ulcerative colitis.

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Background: 

5-Aminosalicylates (5-ASA) are considered a first-line therapy for inducing and maintaining remission of mild to moderately active ulcerative colitis (UC). When inflammation in UC is limited to the distal colon, 5-ASA can also be administered rectally as a suppository, enema or foam.

Objectives: 

A systematic review was undertaken to evaluate the efficacy of rectal 5-ASA for treating active distal UC.

Search strategy: 

Electronic searches of the MEDLINE database (1966-2008), the Cochrane Central Register of Controlled Trials and the Cochrane IBD/FBD Group Specialized Trials Register were supplemented by manual reviews of reference listings and conference proceedings.

Selection criteria: 

Randomized trials comparing rectal 5-ASA to placebo or another active therapy were eligible for inclusion. Eligible trials enrolled patients with a distal disease margin less than 60 cm from the anal verge or distal to the splenic flexure. Trials that enrolled subjects less than 12 years of age were excluded.

Data collection and analysis: 

Eligibility was assessed by three authors. Data were extracted by two authors using standardized forms. Pooled odds ratios (POR) for inducing improvement and remission by symptomatic, endoscopic and histologic criteria were calculated using an intention to treat principle. Fixed effects models were used unless heterogeneity was encountered within groups (P < 0.10), where random effects models were used. All statistical analyses were performed using RevMan 5. Where sufficient data were available, subgroup analyses were performed for disease extent, total daily 5-ASA dose, 5-ASA formulation (enema,suppository, foam) and the type of control intervention (placebo or another active therapy).

Main results: 

Thirty-eight studies fulfilled the inclusion criteria. Rectal 5-ASA was superior to placebo for inducing symptomatic, endoscopic and histological improvement and remission, with POR for symptomatic improvement 8.87 (8 trials, 95% CI: 5.30 to 14.83; P < 0.00001), endoscopic improvement 11.18 (5 trials, 95% CI 5.99 to 20.88; P < 0.00001), histologic improvement 7.69 (6 trials, 95% CI 3.26 to 18.12; P < 0.00001), symptomatic remission 8.30 (8 trials, 95% CI 4.28 to 16.12; P < 0.00001), endoscopic remission 5.31 (7 trials, 95% CI 3.15 to 8.92; P < 0.00001), and histologic remission 6.28 (5 trials, 95% CI 2.74 to 14.40; P < 0.0001). Rectal 5-ASA was superior to rectal corticosteroids for inducing symptomatic improvement and remission with POR 1.56 (6 trials, 95% CI 1.15 to 2.11; P = 0.004) and 1.65 (6 trials, 95% CI 1.11 to 2.45; P = 0.01), respectively. Rectal 5-ASA was not superior to oral 5-ASA for symptomatic improvement (POR 2.25; 95% CI 0.53 to 19.54; P = 0.27). Neither total daily dose nor 5-ASA formulation affected treatment response.

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