Background

Clinicians, patients, payers and policymakers require relevant, high-quality evidence to support decision-making regarding the treatment of ulcerative colitis (UC). In the absence of head-to-head trials, network meta-analysis (NMA) can be used to compare treatments. We conducted an NMA to compare the efficacy of ontamalimab (anti-MAdCAM-1) using its phase 2 data, with all biologics and novel small molecules for which induction study data on endoscopic response were available.

Methods

A systematic literature review was conducted in November 2017 to identify published randomised controlled trials of induction treatment in patients with moderate-to-severe UC. An NMA of the identified studies was performed using random-effects models and methods based on NICE guidance. Odds ratios and 95% credible intervals were calculated to describe the relative differences between treatments and placebo in terms of efficacy in inducing endoscopic response. Results were examined by anti-TNF status (naïve vs. experienced).

Results

In total, 15 phase 2 and phase 3 induction studies of the following agents were available and included: adalimumab (160/80mg), etrolizumab (100mg and 300mg), golimumab (200/100mg), infliximab (5mg), ontamalimab (22.5mg and 75mg), ozanimod (0.5mg and 1mg), tofacitinib (10mg) and vedolizumab (300mg). The definition of endoscopic response (improvement) in all trials was a Mayo endoscopic subscore of ≤1. Homogeneity between studies was good, enabling pooling of results. Figure 1 shows odds ratios for induction of endoscopic response with treatments relative to placebo in anti-TNF-naïve and -experienced patients. All treatments performed significantly better than placebo in anti-TNF-naïve patients, with the exception of both doses of etrolizumab and ozanimod 0.5 mg. Significant differences between some treatments were observed; specifically, ontamalimab 22.5 mg (p = 0.0277), tofacitinib 10 mg (p = 0.0233) and infliximab 5 mg (p = 0.0047) were all superior to adalimumab 160/80 mg.

Conclusion

This study suggests that ontamalimab, infliximab and tofacitinib could be superior to adalimumab in inducing endoscopic healing, although it was conducted before any large-scale head-to-head trials of these drugs. Furthermore, large variances due to differing endpoint timings, the combination of phase 2 and phase 3 data, and lack of control for placebo response rates preclude firm conclusions being drawn.

中文翻译：

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P463内镜反应的诱导：诱导研究的网络荟萃分析，比较了Ontamalimab与其他治疗中至重度溃疡性结肠炎的方法

背景

临床医生，患者，付款人和决策者需要相关的高质量证据来支持有关溃疡性结肠炎（UC）治疗的决策。在没有进行头对头试验的情况下，网络荟萃分析（NMA）可用于比较治疗方法。我们进行了一次NMA，以比较其第二阶段数据与ontamalimab（anti-MAdCAM-1）的功效，以及所有生物制剂和新颖的小分子的内镜反应诱导研究数据，它们的有效性。

方法

2017年11月进行了系统的文献综述，以鉴定已发表的中度至重度UC患者的诱导治疗随机对照试验。使用随机效应模型和方法（基于NICE指导）对确定的研究进行NMA。计算几率和95％可信区间以描述治疗和安慰剂之间在诱导内窥镜反应中的功效方面的相对差异。通过抗TNF状态检查结果（未处理vs.经验）。

结果

总共进行了以下药物的15项2期和3期诱导研究，包括：阿达木单抗（160 / 80mg），埃特罗珠单抗（100mg和300mg），戈利木单抗（200 / 100mg），英夫利昔单抗（5mg），奥坦单抗（22.5mg和75mg），ozanimod（0.5mg和1mg），tofacitinib（10mg）和vedolizumab（300mg）。所有试验中内镜反应（改善）的定义为Mayo内镜评分≤1。研究之间的同质性很好，可以合并结果。图1显示了相对于安慰剂安慰剂治疗的抗TNF初治和有经验的患者诱导内窥镜反应的优势比。在未接受TNF治疗的患者中，所有治疗均优于安慰剂，但两种剂量的埃托珠单抗和ozanimod的剂量均为0.5 mg。观察到一些治疗之间的显着差异。特别，

结论

这项研究表明，尽管在进行这些药物的任何大规模的头对头试验之前，ontamalimab，infliximab和tofacitinib在诱导内镜愈合方面可能优于阿达木单抗。此外，由于不同的终点时机，2期和3期数据的组合以及对安慰剂反应率缺乏控制而导致的较大差异，无法得出明确的结论。