Sutherland L, MacDonald J K
Division of Gastroenterology, University of Calgary, Foothills Hospital, 1751 3330 Hospital Drive N W, Calgary, AB, Canada, T2N 4N1.
Cochrane Database Syst Rev. 2003(3):CD000543. doi: 10.1002/14651858.CD000543.
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 2g/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.
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.
A computer-assisted literature search for relevant studies (1981-2003) 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.
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.
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.
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 0.51 (95% CI, 0.35 to 0.76). A dose-response trend for 5-ASA was also observed. When 5-ASA was compared to SASP, the pooled Peto odds ratio was 0.87 (CI, 0.63 to 1.21) for the failure to induce global/clinical improvement or remission, and 0.66 (CI, 0.42 to 1.04) for the failure to induce endoscopic improvement. SASP was not as well tolerated as 5-ASA.
REVIEWER'S 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 2, 2003).
新型5-氨基水杨酸（5-ASA）制剂旨在避免柳氮磺胺吡啶（SASP）的不良反应，同时保留其治疗益处。众多临床试验对5-ASA制剂的疗效和安全性进行了评估，但这些试验往往缺乏足够的统计学效力以得出明确结论。此前发现，剂量至少为2g/天的新型5-ASA药物在诱导溃疡性结肠炎缓解方面比安慰剂更有效，但不比SASP更有效。本更新综述纳入了更多近期研究，并根据更精确的结局指标评估了5-ASA制剂的有效性、剂量反应性和安全性。
评估新型释放剂型的5-氨基水杨酸（5-ASA）与安慰剂或柳氮磺胺吡啶（SASP）相比，在诱导活动性溃疡性结肠炎缓解方面的疗效、剂量反应性和安全性。
使用MEDLINE、BIOS、Cochrane对照试验注册库、Cochrane炎症性肠病组专业试验注册库和科学引文索引对相关研究（1981 - 2003年）进行计算机辅助文献检索，随后手动检索先前检索文章的参考文献列表、综述文章、研讨会论文集以及主要胃肠病学会议的摘要。
若研究为随机、双盲、平行设计的对照临床试验，治疗持续时间至少四周，则纳入分析。
基于意向性分析原则，治疗活动性疾病时关注的结局为未能诱导整体/临床缓解、整体/临床改善、内镜缓解或内镜改善。
在所有测量的结局变量方面，5-ASA均优于安慰剂。对于未能诱导整体/临床改善或缓解，合并的Peto比值比为0.51（95%CI，0.35至- 0.76）。还观察到5-ASA的剂量反应趋势。当将5-ASA与SASP比较时，对于未能诱导整体/临床改善或缓解，合并的Peto比值比为0.87（CI，0.63至1.21），对于未能诱导内镜改善，比值比为0.66（CI，0.42至1.04）。SASP的耐受性不如5-ASA。
新型5-ASA制剂优于安慰剂，且在治疗益处上倾向于超过SASP。然而，考虑到它们的相对成本，用新型5-ASA制剂替代SASP在临床上似乎不太可能具有优势。本综述更新了发表在《Cochrane图书馆》（2003年第2期）中关于口服5-氨基水杨酸诱导溃疡性结肠炎缓解的现有综述。
