Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis.

Background: The newer 5-ASA preparations were intended to avoid the adverse effects of SASP while maintaining its therapeutic benefits. The efficacy and safety of 5-ASA preparations have been evaluated in numerous clinical trials that have often lacked sufficient statistical power to arrive at definitive conclusions. Previously, it was found that newer 5-ASA drugs were more effective than placebo but no more effective than SASP in inducing remission in ulcerative colitis. This updated review includes more recent studies and evaluates the effectiveness, dose-responsiveness, and safety of 5-ASA preparations in terms of more precise outcome measures.

Objectives: To assess the efficacy, dose-responsiveness and safety of the newer release formulations of 5-aminosalicylic acid (5-ASA) compared to placebo or sulfasalazine (SASP) in the maintenance of remission in ulcerative colitis.

Search Strategy: A computer-assisted literature search for relevant studies (1981-2002) was performed using MEDLINE, BIOS, the Cochrane Controlled Trials Register, the Cochrane IBD Group Specialized Trials Register, and the Science Citation Index, followed by a manual search of reference lists from previously retrieved articles, review articles, symposia proceedings, and abstracts from major gastrointestinal conferences.

Selection Criteria: Studies were accepted for analysis if they were prospective, randomized, double-blinded, and placebo- or SASP-controlled clinical trials of parallel design with treatment duration of at least six months.

Data Collection And Analysis: Based on an intention to treat principle, the primary outcome was the failure to maintain clinical or endoscopic remission. Secondary outcomes were the number of patients experiencing adverse events, the number of patients withdrawn due to adverse events, and exclusions or withdrawals after entry into the study (not due to relapse). All data were analyzed using the Peto odds ratio and corresponding 95% confidence intervals (CI).

Main Results: The Peto odds ratio for the failure to maintain clinical or endoscopic remission (withdrawals and relapses) for 5-ASA versus placebo was 0.47 (95% CI, 0.36 to 0.62) with an NNT of 6. These values were also calculated for the trials in which SASP and 5-ASA were compared, revealing an odds ratio of 1.29 (95% CI, 1.05 to 1.57), with a negative NNT value (-19), suggesting a higher degree of therapeutic effectiveness for SASP. SASP and 5-ASA had similar adverse event profiles, with odds ratios of 1.16(0.62 to 2.16), and 1.31(0.86 to 1.99), respectively. The NNH values were determined to be 171 and 78 respectively.

Reviewer's Conclusions: The newer 5-ASA preparations were superior to placebo in maintenance therapy. However, the newer preparations had a statistically significant therapeutic inferiority relative to SASP. This review updates the existing review of oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis which was published in the Cochrane Library (Issue 3, 2002).