Background

Anti-TNF antibodies treatments are the only first-line reimbursed biologics for Crohn’s disease (CD) in several countries. Recently, Vedolizumab (VDZ) and Ustekinumab (UST) were added to the therapeutic armamentarium for CD refractory to a first anti-TNF antibody. However, studies comparing these two compounds remain unavailable. Our aim was to compare their efficacy in second-line treatment in CD after failure of one TNF antagonist.

Methods

All patients with CD refractory (primary or secondary non-responders) to first anti-TNF treatment and receiving UST or VDZ as a second biologic were included retrospectively in 10 French tertiary centres. The remission and clinical response were assessed at week 14. On the long-term, the cumulative probabilities of being in remission were estimated using the Kaplan–Meier method and the associated factors using a Cox proportional risk model. The drug survival to assess efficacy as well as side effects was assessed by actuarial analysis.

Results

88 patients were included, 50 (57%) females (mean age: 41 ± 15 years), 61 (69%) being treated with UST and 27 (31%) with VDZ. The first anti-TNF was discontinued for primary or secondary non-response in 66 (75%) patients and for side effects in 22 (25%) patients, without any difference between the anti-TNF antibody previously used. Among the 55 patients with endoscopic data at baseline, 55 (98%) had ulceration, a CRP above 5mg/l for 33/71 (46%) patients and a faecal calprotectin > 250 µg/g for the 12 patients tested. At week 14, no difference was observed for clinical response and clinical remission according to the type of treatment: the rate of clinical response and remission were 74% (UST)/58% (VDZ) (p = 0.20) and 33% (UST)/26% (VDZ) (p = 0.56), respectively. The only factor associated with short-term remission was the lack of optimisation prior to anti-TNF discontinuation (p = 0.038) regardless of the type of second-line therapy (UST, p = 0.02; VDZ, p = 0.03). After a mean follow-up of 67 weeks, the cumulative probabilities of being in remission at 6 and 12 months were 16% and 34% for UST and 25% and 44% for VDZ, respectively (p = 0.24 for UST vs. VDZ). The drug survival was higher in the UST group as compared with the VDZ group (HR (UST vs. VDZ) = 2.36 [1.02–5.5], p = 0.04).

Conclusion

Our preliminary results suggest that VDZ and UST have similar efficacy in the short- and long-term response when used as a second-line biologic therapy in CD refractory to a first anti-TNF antibody. These results will be complemented for the congress by the inclusion of additional patients recruited into this registry.

中文翻译：

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P665克罗恩病期间抗TNF失败后的第二线生物学药物：Ustekinumab或vedolizumab，一项多中心回顾性研究

背景

抗TNF抗体治疗是一些国家唯一的克罗恩病（CD）报销的一线生物制剂。最近，将维多珠单抗（VDZ）和乌斯他单抗（UST）添加到治疗性武器库中，使第一抗TNF抗体难治的CD。但是，尚无法进行比较这两种化合物的研究。我们的目的是比较一种TNF拮抗剂失败后在CD二线治疗中的疗效。

方法

在法国的10个三级中心对所有对CD难治性（主要或继发性无反应者）首次抗TNF治疗且接受UST或VDZ作为第二生物制剂的患者进行回顾性研究。在第14周评估缓解和临床反应。从长期来看，使用Kaplan-Meier方法评估缓解的累积概率，并使用Cox比例风险模型评估相关因素。通过精算分析评估药物存活率以评估功效和副作用。

结果

其中包括88名患者，其中50名（57％）女性（平均年龄：41±15岁），61名（69％）接受UST治疗和27名（31％）接受VDZ治疗。第66例（75％）患者的原发性或继发性无反应和22例（25％）的患者中止了第一种抗TNF，以前使用的抗TNF抗体之间没有任何差异。在基线时有内窥镜检查数据的55例患者中，有55例（98％）有溃疡，33/71例（46％）患者的CRP高于5mg / l，而12例患者的粪便钙卫蛋白> 250 µg / g。在第14周，根据治疗类型，临床反应和临床缓解无差异：临床反应和缓解率分别为74％（UST）/ 58％（VDZ）（p = 0.20）和33％（UST ）/ 26％（VDZ）（p = 0.56）。与短期缓解相关的唯一因素是，无论采用哪种二线治疗（UST，p = 0.02； VDZ，p = 0.03），抗-TNF终止前均缺乏优化（p = 0.038）。经过平均67周的随访后，在6个月和12个月时缓解的累积概率分别为UST的16％和34％，VDZ的25％和44％（UST vs. VDZ p = 0.24） 。与VDZ组相比，UST组的药物生存率更高（HR（UST与VDZ）= 2.36 [1.02-5.5]，p = 0.04）。

结论

我们的初步结果表明，VDZ和UST用作抗一抗TNF抗体的CD的二线生物疗法时，在短期和长期反应中具有相似的功效。这些结果将通过增加招募到该注册表的其他患者来补充。