Sutherland L, Macdonald J K
Cochrane Database Syst Rev. 2006 Apr 19(2):CD000544. doi: 10.1002/14651858.CD000544.pub2.
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.
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.
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.
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.
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 Secondary outcomes were the number of patients experiencing adverse events, the number of patients withdrawn due to adverse events, and exclusions or withdrawals after entry into the study (not due to relapse).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).
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.
AUTHORS' 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 1, 2006).
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，同时保留其治疗效果。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效力以得出明确结论。此前发现，在诱导溃疡性结肠炎缓解方面，新型5-ASA药物比安慰剂更有效，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5-ASA制剂的有效性、剂量反应性和安全性。
评估新型5-氨基水杨酸（5-ASA）制剂与安慰剂或柳氮磺胺吡啶（SASP）相比，在维持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/功能性肠道疾病组专业试验注册库和科学引文索引对相关研究（1981 - 2005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。
如果研究是前瞻性、随机、双盲且采用平行设计的安慰剂或SASP对照临床试验，治疗持续时间至少为6个月，则纳入分析。
基于意向性治疗原则，主要结局是未能维持临床或内镜缓解。次要结局是发生不良事件的患者数量、因不良事件退出的患者数量以及进入研究后（非因复发）的排除或退出情况。所有数据使用Peto比值比及相应的95%置信区间（CI）进行分析。
5-ASA与安慰剂相比，未能维持临床或内镜缓解（退出和复发）的Peto比值比为0.47（95%CI，0.36至0.62），需治疗人数（NNT）为6。在比较SASP和5-ASA的试验中也计算了这些值，得出比值比为1.29（95%CI，1.05至1.57），需治疗人数为负值（-19），表明SASP的治疗效果更高。SASP和5-ASA的不良事件谱相似，比值比分别为1.16（0.62至2.16）和1.31（0.86至1.99）。确定的伤害需治疗人数（NNH）值分别为171和78。
新型5-ASA制剂在维持治疗方面优于安慰剂。然而，相对于SASP，新型制剂在统计学上具有显著的治疗劣势。本综述更新了发表在Cochrane图书馆（2006年第1期）的关于口服5-氨基水杨酸维持溃疡性结肠炎缓解的现有综述。
