Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
Division of Biomedical Informatics, University of California San Diego, La Jolla, CA, USA.
Aliment Pharmacol Ther. 2018 Jan;47(2):162-175. doi: 10.1111/apt.14422. Epub 2017 Dec 4.
There are limited data to inform positioning of agents for treating moderate-severe ulcerative colitis (UC).
To assess comparative efficacy and safety of different therapies as first-line (biologic-naïve) and second-line (prior exposure to anti-tumour necrosis factor(TNF)-α) agents for moderate-severe UC, through a systematic review and network meta-analysis, and appraise quality of evidence (QoE) using grading of recommendations, assessment, development and evaluation (GRADE) approach.
We identified randomised controlled trials (RCTs) in adults with moderate-severe UC treated with anti-TNF agents, anti-integrin agents and janus kinase (JAK) inhibitors, as first-line or second-line agents, and compared with placebo or another active agent. Efficacy outcomes were induction/maintenance of remission and mucosal healing; and safety outcomes were serious adverse events and infections. Network meta-analyses were performed, and ranking was assessed using surface under the cumulative ranking (SUCRA) probabilities.
In biologic-naïve patients (12 trials, no head-to-head comparisons), infliximab and vedolizumab were ranked highest for induction of clinical remission (infliximab: odds ratio [OR], 4.10 [95% confidence intervals [CI], 2.58-6.52]; SUCRA,0.85; vedolizumab:SUCRA,0.82) and mucosal healing (infliximab:SUCRA,0.91; vedolizumab:SUCRA,0.81) (moderate QoE). In patients with prior anti-TNF exposure (4 trials, no head-to-head comparisons), tofacitinib was ranked highest for induction of clinical remission (OR, 11.88 [2.32-60.89]; SUCRA, 0.96) and mucosal healing (moderate QoE). Differences in trial design limited comparability of trials of maintenance therapy for efficacy. Vedolizumab was ranked safest in terms of serious adverse events (SUCRA, 0.91), and infection (SUCRA, 0.75) in maintenance trials.
Infliximab and vedolizumab are ranked highest as first-line agents, and tofacitinib is ranked highest as second-line agent, for induction of remission and mucosal healing in patients with moderate-severe UC, based on indirect comparisons. Head-to-head trials are warranted to inform clinical decision-making with greater confidence.
目前用于治疗中重度溃疡性结肠炎（UC）的药物定位数据有限。
通过系统评价和网络荟萃分析，评估不同治疗方法作为中重度 UC 一线（生物初治）和二线（先前使用抗 TNF-α 药物）治疗药物的疗效和安全性，并使用推荐评估、制定与评价（GRADE）方法评估证据质量（QoE）。
我们检索了成人中重度 UC 患者使用 TNF 拮抗剂、整合素拮抗剂和 JAK 抑制剂作为一线或二线治疗药物的随机对照试验（RCT），并将其与安慰剂或其他活性药物进行比较。疗效终点为诱导缓解/维持缓解和黏膜愈合；安全性终点为严重不良事件和感染。进行网络荟萃分析，并使用累积排序概率曲线下面积（SUCRA）评估排序。
在生物初治患者（12 项试验，无头对头比较）中，英夫利昔单抗和维得利珠单抗在诱导临床缓解方面的排名最高（英夫利昔单抗：比值比[OR]，4.10[95%置信区间[CI]，2.58-6.52]；SUCRA，0.85；维得利珠单抗：SUCRA，0.82）和黏膜愈合（英夫利昔单抗：SUCRA，0.91；维得利珠单抗：SUCRA，0.81）（中质量 QoE）。在有既往抗 TNF 暴露的患者（4 项试验，无头对头比较）中，托法替布在诱导临床缓解方面的排名最高（OR，11.88[2.32-60.89]；SUCRA，0.96）和黏膜愈合（中质量 QoE）。由于试验设计的差异，维持治疗疗效的试验可比性有限。在维持治疗的严重不良事件（SUCRA，0.91）和感染（SUCRA，0.75）方面，维得利珠单抗的安全性排名最高。
基于间接比较，英夫利昔单抗和维得利珠单抗是中重度 UC 患者一线治疗药物中缓解和黏膜愈合的最佳选择，而托法替布是二线治疗药物中缓解和黏膜愈合的最佳选择。需要进行头对头试验，以更有信心地为临床决策提供信息。
