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 in doses of at least 2 g/day, 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) for the induction of remission in active ulcerative colitis. SEARCH STRATEGY: A computer-assisted literature search for relevant studies (1981-2005) was performed using MEDLINE, BIOS, the Cochrane Controlled Trials Register, the Cochrane IBD/FBD 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 randomized, double-blinded, and controlled clinical trials of parallel design, with treatment durations of a minimum of four weeks. DATA COLLECTION AND ANALYSIS: Based on an intention to treat principle, the outcomes of interest in the treatment of active disease were the failure to induce global/clinical remission, global/clinical improvement, endoscopic remission, or endoscopic improvement. MAIN RESULTS: 5-ASA was superior to placebo with regard to all measured outcome variables. For the failure to induce global/clinical improvement or remission, the pooled Peto odds ratio was 0.40 (95% CI, 0.30 to 0.53). A dose-response trend for 5-ASA was also observed. When 5-ASA was compared to SASP, the pooled Peto odds ratio was 0.83 (95% CI 0.60 to 1.13) for the failure to induce global/clinical improvement or remission, and 0.66 (95% CI 0.42 to 1.04) for the failure to induce endoscopic improvement. SASP was not as well tolerated as 5-ASA. AUTHORS' CONCLUSIONS: The newer 5-ASA preparations were superior to placebo and tended towards therapeutic benefit over SASP. However, considering their relative costs, a clinical advantage to using the newer 5-ASA preparations in place of SASP appears unlikely. This review updates the existing review of oral 5-aminosalicylic acid for induction of remission in ulcerative colitis which was published in the Cochrane Library (Issue 1, 2006).
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 in doses of at least 2 g/day, 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) for the induction of remission in active ulcerative colitis. SEARCH STRATEGY: A computer-assisted literature search for relevant studies (1981-2005) was performed using MEDLINE, BIOS, the Cochrane Controlled Trials Register, the Cochrane IBD/FBD 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 randomized, double-blinded, and controlled clinical trials of parallel design, with treatment durations of a minimum of four weeks. DATA COLLECTION AND ANALYSIS: Based on an intention to treat principle, the outcomes of interest in the treatment of active disease were the failure to induce global/clinical remission, global/clinical improvement, endoscopic remission, or endoscopic improvement. MAIN RESULTS:5-ASA was superior to placebo with regard to all measured outcome variables. For the failure to induce global/clinical improvement or remission, the pooled Peto odds ratio was 0.40 (95% CI, 0.30 to 0.53). A dose-response trend for 5-ASA was also observed. When 5-ASA was compared to SASP, the pooled Peto odds ratio was 0.83 (95% CI 0.60 to 1.13) for the failure to induce global/clinical improvement or remission, and 0.66 (95% CI 0.42 to 1.04) for the failure to induce endoscopic improvement. SASP was not as well tolerated as 5-ASA. AUTHORS' CONCLUSIONS: The newer 5-ASA preparations were superior to placebo and tended towards therapeutic benefit over SASP. However, considering their relative costs, a clinical advantage to using the newer 5-ASA preparations in place of SASP appears unlikely. This review updates the existing review of oral 5-aminosalicylic acid for induction of remission in ulcerative colitis which was published in the Cochrane Library (Issue 1, 2006).