ABSTRACT

Objectives: Because only one head-to-head randomized trial of biologics for moderate-to-severe UC has been performed, indirect treatment comparisons remain important. This systematic review and network meta-analysis examined efficacy and safety of biologics and tofacitinib for moderate-to-severe UC, using vedolizumab as reference.

Methods: Relevant studies (N = 19) of vedolizumab, adalimumab, infliximab, golimumab, ustekinumab, and tofacitinib were identified. Study design differences were addressed by assessing efficacy outcomes conditional on response at maintenance initiation. Primary analysis used fixed-effect models to estimate odds ratios for efficacy and safety endpoints.

Results: Compared with vedolizumab 300 mg, adalimumab 160/80 mg was associated with less clinical remission (odds ratio, 0.69 [95% credible interval, 0.54–0.88]), and infliximab 5 mg/kg was associated with more clinical remission (1.67 [1.16–2.42]) and response (1.63 [1.15–2.30]). Adalimumab 40 mg, golimumab 50 mg, and ustekinumab 90 mg Q12W had significantly lower clinical remission rates during maintenance (0.62 [0.45–0.86], 0.55 [0.32–0.95], and 0.59 [0.35–0.99]) versus vedolizumab 300 mg Q8W. Response results were similar. Tofacitinib 10 mg had the highest maintenance treatment efficacy estimates and highest infection risk.

Conclusion: Network meta-analysis and novel integrated benefit-risk analysis suggest a potentially favorable efficacy-safety balance for vedolizumab vs adalimumab and other advanced UC therapies.

摘要

目标：因为只进行了一项针对中重度 UC 的生物制剂头对头随机试验，间接治疗比较仍然很重要。本系统评价和网络荟萃分析使用维多珠单抗作为参考，检查了生物制剂和托法替尼对中重度 UC 的疗效和安全性。

方法：确定了维多珠单抗、阿达木单抗、英夫利昔单抗、戈利木单抗、优特克单抗和托法替尼的相关研究（N = 19）。通过评估以维持治疗开始时的反应为条件的疗效结果来解决研究设计差异。主要分析使用固定效应模型来估计疗效和安全性终点的优势比。

结果：与维多珠单抗 300 mg 相比，阿达木单抗 160/80 mg 与较少的临床缓解相关（优势比，0.69 [95% 可信区间，0.54–0.88]），而英夫利昔单抗 5 mg/kg 与更多的临床缓解相关（1.67 [1.16–2.42]) 和响应 (1.63 [1.15–2.30])。阿达木单抗 40 毫克、戈利木单抗 50 毫克和优特克单抗 90 毫克 Q12W 在维持期间的临床缓解率显着降低（0.62 [0.45–0.86]、0.55 [0.32–0.95] 和 0.59 [0.35–0.99]）与 3.0W 维多珠单抗相比 响应结果相似。托法替尼 10 mg 具有最高的维持治疗疗效估计值和最高的感染风险。

结论：网络荟萃分析和新的综合收益-风险分析表明，维多珠单抗与阿达木单抗和其他先进的 UC 疗法具有潜在的有利疗效-安全平衡。