Alternatives to sulfasalazine: A meta-analysis of 5-ASA in the treatment of ulcerative colitis

The purpose of this study was to assess the efficacy and safety of the newer release formulations of 5-aminosalicylic acid (5-ASA) compared with placebo or sulfasalazine (SASP) for the treatment of active disease and the maintenance of remission in ulcerative colitis. A computer-assisted literature search for relevant studies (1981-1996) was performed using MEDLINE, BIOS, and 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. 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 4 weeks for the treatment of active disease (19 studies), and a minimum of 6 months for maintenance therapy (16 studies). 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. For maintenance therapy, the primary measured outcome was the failure to maintain clinical or endoscopic remission. In active disease, 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 odds ratio was 0.39 [95% confidence interval (CI), 0.29-0.52]. A dose-response trend for 5-ASA was also observed. When 5-ASA was compared with SASP in active disease, the pooled odds ratio was 0.87 (CI, 0.63-1.20) for the failure to induce global/clinical improvement or remission, and 0.66 (CI, 0.42-1.04) for the failure to induce endoscopic improvement. In maintenance therapy, the pooled odds ratio for the failure to maintain clinical or endoscopic remission (withdrawals and relapses) for 5-ASA versus placebo was 0.48 (CI, 0.35-0.65) and versus SASP, 1.29 (CI, 1.06-1.57) at 6 months and 1.15 (0.89-1.50) at 12 months. SASP was not as well tolerated as 5-ASA in active disease despite their relatively similar tolerabilities in maintenance therapy. The newer 5-ASA preparations were superior to placebo for both active disease and maintenance of remission. In a patient population selected for tolerance to SASP, there is insufficient evidence to confirm their benefit over SASP for either active or maintenance therapy.