Department of Surgery, Oncology and Gastroenterology [DISCOG], Gastroenterology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy.
Department of Gastroenterology and Hepatology, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK.
J Crohns Colitis. 2021 Jul 5;15(7):1184-1196. doi: 10.1093/ecco-jcc/jjab010.
5-Aminosalicylates [5-ASAs] are the mainstay of treatment for ulcerative colitis [UC]. The optimum preparation, dose, and route of administration for UC remain unclear. We conducted a network meta-analysis to examine this issue.
We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials from inception to December 2020. We included randomised controlled trials [RCTs] comparing oral, topical, or combined oral and topical 5-ASAs, with each other or placebo for induction of remission or prevention of relapse of UC. Results were reported as pooled relative risks [RRs] with 95% confidence intervals [CIs] to summarise effect of each comparison tested, with treatments ranked according to P-score.
We identified 40 RCTs for induction of remission and 23 for prevention of relapse. Topical mesalazine [P-score 0.99], or oral and topical mesalazine combined [P-score 0.87] ranked first and second for clinical and endoscopic remission combined. Combined therapy ranked first in trials where ≥50% of patients had left-sided/extensive disease, and topical mesalazine first in trials where ≥50% of patients had proctitis/proctosigmoiditis. High-dose [≥3.3 g/day] oral mesalazine ranked third in most analyses, with the most trials and most patients. For relapse of disease activity, combined therapy and high-dose oral mesalazine ranked first and second, with topical mesalazine third. 5-ASAs were safe and well tolerated, regardless of regimen.
Our results support previous evidence; however, higher doses of oral mesalazine had more evidence for induction of remission than combined therapy and were significantly more efficacious than lower doses. Future RCTs should better establish the role of combined therapy for induction of remission, as well as optimal doses of oral 5-ASAs to prevent relapse.
5-氨基水杨酸（5-ASA）是治疗溃疡性结肠炎（UC）的主要药物。对于 UC，最佳的制剂、剂量和给药途径仍不明确。我们进行了一项网状荟萃分析来探讨这个问题。
我们检索了 MEDLINE、EMBASE、EMBASE Classic 和 Cochrane 对照试验中心注册库，从建库至 2020 年 12 月。我们纳入了比较口服、局部或口服联合局部 5-ASA 制剂与安慰剂治疗 UC 诱导缓解或预防复发的随机对照试验（RCT）。结果以汇总相对风险（RR）和 95%置信区间（CI）表示，以总结每一种比较的疗效，治疗方法按 P 评分排序。
我们共纳入了 40 项诱导缓解和 23 项预防复发的 RCT。局部美沙拉嗪（P 评分 0.99）或口服和局部美沙拉嗪联合（P 评分 0.87）在临床和内镜缓解联合方面排名第一和第二。联合治疗在≥50%的患者患有左半结肠/广泛疾病的试验中排名第一，局部美沙拉嗪在≥50%的患者患有直肠乙状结肠炎的试验中排名第一。高剂量（≥3.3 g/天）口服美沙拉嗪在大多数分析中排名第三，纳入的试验和患者最多。对于疾病活动的复发，联合治疗和高剂量口服美沙拉嗪排名第一和第二，局部美沙拉嗪排名第三。无论治疗方案如何，5-ASA 都是安全且耐受良好的。
我们的结果支持既往的证据；然而，高剂量的口服美沙拉嗪在诱导缓解方面的证据比联合治疗更多，且疗效显著优于低剂量。未来的 RCT 应更好地确定联合治疗在诱导缓解方面的作用，以及预防复发时口服 5-ASA 的最佳剂量。
