Lanzhou University, Lanzhou, China.
Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.
Medicine (Baltimore). 2023 Oct 27;102(43):e35689. doi: 10.1097/MD.0000000000035689.
Biological agents are commonly used for the first-line treatment of ulcerative colitis (UC). However, small-molecule drugs and microbiome therapies are now being used as new treatments for ulcerative colitis. We aimed to compare the relative efficacy and safety of biologics, small-molecule drugs, and microbiome therapies for the treatment of patients with moderate-to-severe ulcerative colitis.
We searched the Cochrane, Embase, and PubMed databases from their inception to December 2022. RCTs that recruited patients with moderate-to-severe ulcerative colitis treated with biological agents, small-molecule drugs, and microbiome therapies. Efficacy outcomes were induction of clinical remission and mucosal healing; safety outcomes were adverse events and serious adverse events. A network meta-analysis with multivariate consistency model random-effect meta-regression was done, with rankings based on surface under the cumulative ranking curve (SUCRA) values. Higher SUCRA scores correlate with better efficacy, whereas lower SUCRA scores correlate with better safety.
A total of 31 RCTs comprising 7933 UC patients were included in our studies. A risk of bias assessment showed a low risk of bias for most of the included studies. Upadacitinib ranked highest for induction of clinical remission (SUCRA, 0.83) and mucosal healing (SUCRA, 0.44). Moreover, no treatments were found to increase the occurrence of adverse events compared with placebos. Ustekinumab ranked lowest for adverse events (SUCRA 0.26) and probiotic ranked lowest for serious adverse events (0·21), whereas tofacitinib ranked highest for adverse events (0·43) and upadacitinib ranked highest for serious adverse events (0·43).
In this systematic review and network meta-analysis, we found upadacitinib to be ranked highest for the induction of clinical remission and mucosal healing, but the worst performing agent in terms of adverse events in UC patients. Probiotics were the best-performing agent for safety outcomes. More trials of direct comparisons are needed to inform clinical decision-making with greater confidence.
生物制剂常用于溃疡性结肠炎（UC）的一线治疗。然而，小分子药物和微生物组疗法现在被用作溃疡性结肠炎的新治疗方法。我们旨在比较生物制剂、小分子药物和微生物组疗法治疗中重度溃疡性结肠炎患者的相对疗效和安全性。
我们从成立到 2022 年 12 月在 Cochrane、Embase 和 PubMed 数据库中进行了搜索。RCT 招募了接受生物制剂、小分子药物和微生物组疗法治疗的中重度溃疡性结肠炎患者。疗效结局为诱导临床缓解和黏膜愈合；安全性结局为不良事件和严重不良事件。采用多变量一致性模型随机效应荟萃回归的网络荟萃分析，并基于排序累积排名曲线下面积（SUCRA）值进行排名。较高的 SUCRA 分数与更好的疗效相关，而较低的 SUCRA 分数与更好的安全性相关。
共有 31 项 RCT 纳入了 7933 名 UC 患者。偏倚风险评估显示，大多数纳入研究的偏倚风险较低。Upadacitinib 在诱导临床缓解（SUCRA，0.83）和黏膜愈合（SUCRA，0.44）方面排名最高。此外，与安慰剂相比，没有治疗方法被发现会增加不良事件的发生。Ustekinumab 在不良事件方面排名最低（SUCRA 0.26），益生菌在严重不良事件方面排名最低（0·21），而托法替尼在不良事件方面排名最高（0·43），Upadacitinib 在严重不良事件方面排名最高（0·43）。
在这项系统评价和网络荟萃分析中，我们发现 Upadacitinib 在诱导临床缓解和黏膜愈合方面排名最高，但在 UC 患者中不良事件发生率最高。益生菌在安全性结局方面表现最好。需要更多的直接比较试验来更有信心地为临床决策提供信息。
