Background & Aims

We compared the efficacy and safety of different first-line (biologic-naïve) and second-line (prior exposure to tumor necrosis factor [TNF] antagonists) agents for treatment of moderate to severely active ulcerative colitis in a systematic review and network meta-analysis.

Methods

We searched publication databases through September 30, 2019, for randomized trials of adults with moderate to severe ulcerative colitis treated with TNF antagonists, vedolizumab, tofacitinib, or ustekinumab, as first-line or second-line agents, compared with placebo or another active agent. Efficacy outcomes were induction and maintenance of remission and endoscopic improvement; safety outcomes were serious adverse events and infections. We performed a fixed-effects network meta-analysis using the frequentist approach, and calculated odds ratios (ORs) and 95% CI values. Agents were ranked using surface under the cumulative ranking (SUCRA) probabilities. Overall quality of evidence was rated using GRADE (Grading of Recommendations, Assessment, Development and Evaluation).

Results

In biologic-naïve patients, infliximab was ranked highest for induction of clinical remission (OR vs placebo, 4.07; 95% CI, 2.67–6.21; SUCRA, 0.95) and endoscopic improvement (SUCRA, 0.95) (moderate confidence in estimates [CE]). In patients with prior exposure to TNF antagonists, ustekinumab (SUCRA, 0.87) and tofacitinib (SUCRA, 0.87) were ranked highest for induction of clinical remission and were superior to vedolizumab (ustekinumab vs vedolizumab: OR, 5.99; 95% CI, 1.13–31.76 and tofacitinib vs vedolizumab: OR, 6.18; 95% CI, 1.003–8.00; moderate CE) and adalimumab (ustekinumab vs adalimumab: OR, 10.71; 95% CI, 2.01–57.20 and tofacitinib vs adalimumab: OR, 11.05; 95% CI, 1.79–68.41; moderate CE). Vedolizumab had the lowest risk of infections (SUCRA, 0.81), followed by ustekinumab (SUCRA, 0.63) in maintenance trials.

Conclusions

In a systematic review and network meta-analysis, we found infliximab to be ranked highest in biologic-naïve patients, and ustekinumab and tofacitinib were ranked highest in patients with prior exposure to TNF antagonists, for induction of remission and endoscopic improvement in patients with moderate to severe ulcerative colitis. More trials of direct comparisons are needed to inform clinical decision making with greater confidence.

中文翻译：

---

中度至重度活动性溃疡性结肠炎患者的一线和二线药物治疗：更新的网络荟萃分析。

背景与目标

我们通过系统评价和网络荟萃分析，比较了不同一线（生物制剂初治）和二线（之前接触肿瘤坏死因子 [TNF] 拮抗剂）药物治疗中度至重度活动性溃疡性结肠炎的疗效和安全性。分析。

方法

我们检索了截至 2019 年 9 月 30 日的出版物数据库，查找使用 TNF 拮抗剂、维多珠单抗、托法替尼或乌特克单抗作为一线或二线药物与安慰剂或其他活性药物进行比较的成人中度至重度溃疡性结肠炎的随机试验。疗效结果是缓解和维持缓解以及内镜改善；安全性结果是严重的不良事件和感染。我们使用频率论方法进行了固定效应网络荟萃分析，并计算了比值比 (OR) 和 95% CI 值。使用累积排名（SUCRA）概率下的表面对代理进行排名。使用 GRADE（建议、评估、制定和评价分级）对证据的总体质量进行评级。

结果

在未接受过生物制剂治疗的患者中，英夫利昔单抗在诱导临床缓解（OR vs 安慰剂，4.07；95% CI，2.67-6.21；SUCRA，0.95）和内镜改善（SUCRA，0.95）方面排名最高（估计可信度中等[CE]） ）。在既往接触过 TNF 拮抗剂的患者中，乌特克单抗 (SUCRA，0.87) 和托法替布 (SUCRA，0.87) 在诱导临床缓解方面排名最高，且优于维多珠单抗（乌特克单抗 vs 维多珠单抗：OR，5.99；95% CI，1.13– 31.76 和托法替尼 vs 维多珠单抗：OR，6.18；95% CI，1.003–8.00；中度 CE）和阿达木单抗（优特克单抗 vs 阿达木单抗：OR，10.71；95% CI，2.01–57.20 托法替尼 vs 阿达木单抗：OR，11.05；95% CI，1.79–68.41；中等 CE）。在维持试验中，维多珠单抗的感染风险最低（SUCRA，0.81），其次是乌特克单抗（SUCRA，0.63）。

结论

在系统评价和网络荟萃分析中，我们发现英夫利昔单抗在未接受过生物制剂治疗的患者中排名最高，乌特克单抗和托法替布在既往暴露于 TNF 拮抗剂的患者中排名最高，可诱导中度病情患者的缓解和内镜改善。至严重的溃疡性结肠炎。需要更多的直接比较试验才能更有信心地为临床决策提供信息。