Background

Approximately half of patients with Crohn's disease require ileocolonic resection. Of these, 50% will subsequently have endoscopic disease recurrence within 1 year. We aimed to evaluate the efficacy and safety of vedolizumab to prevent postoperative recurrence of Crohn's disease.

Methods

REPREVIO was a double-blind, randomised, placebo-controlled trial conducted at 13 academic or teaching hospitals in France, Italy, the Netherlands, and Spain. Eligible participants were adult patients aged 18 years or older with Crohn's disease who underwent ileocolonic resection and had one or more risk factors for recurrence. Patients were randomly assigned within 4 weeks of surgery (1:1 ratio) to receive intravenous vedolizumab (300 mg) or placebo at weeks 0, 8, 16, and 24. Randomisation was performed centrally with a computer-generated validated variable block model and patients were stratified according to disease behaviour (fibrostenotic vs inflammatory or perforating). Ileocolonoscopy was performed at week 26 and videorecorded. Endoscopic recurrence was centrally assessed with the modified Rutgeerts score, a categorial score ranging from i0 to i4. The primary endpoint was the distribution of modified Rutgeerts scores between treatment groups at week 26, analysed by non-parametric methods. The first-ranked secondary endpoint was the proportion of patients with severe endoscopic recurrence of Crohn's disease at week 26 (modified Rutgeerts score ≥i2b). Primary and safety analyses included all patients who underwent randomisation and received at least one dose of study drug. The trial is registered with the EU Clinical Trial Register (EudraCT; 2015-000555-24).

Findings

Between May 16, 2017, and April 8, 2022, 84 patients were randomly assigned to treatment, of whom four did not receive study treatment, leaving 43 patients in the vedolizumab group and 37 in the placebo group. At week 26, the probability of a lower modified Rutgeerts score with vedolizumab versus placebo was 77·8% (95% CI 66·4 to 86·3; p<0·0001). Severe endoscopic recurrence was observed in ten (23·3%) of 43 patients in the vedolizumab group versus 23 (62·2%) of 37 patients in the placebo group (difference –38·9% [95% CI –56·0 to –17·3]; p=0·0004). Serious adverse events occurred in three (7·0%) of 43 patients who received vedolizumab (bilateral tubo-ovarian abscesses, thrombosed haemorrhoids, and pancreatic adenocarcinoma) and in two (5·4%) of 37 patients who received placebo (intestinal perforation related to Crohn's disease and severe abdominal pain).

Interpretation

Vedolizumab treatment within 4 weeks of ileocolonic resection was more likely to prevent endoscopic Crohn's disease recurrence than placebo, making this an attractive option for postoperative management in patients with risk factors for recurrence. Larger studies with longer follow-up would be desirable.

Funding

Takeda Nederland.

中文翻译：

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维多珠单抗预防克罗恩病术后复发 （REPREVIO）：一项多中心、双盲、随机、安慰剂对照试验

 背景

大约一半的克罗恩病患者需要回肠结肠切除术。其中，50% 的患者随后会在 1 年内出现内窥镜疾病复发。我们旨在评价维多珠单抗预防克罗恩病术后复发的有效性和安全性。

 方法

REPREVIO 是一项双盲、随机、安慰剂对照试验，在法国、意大利、荷兰和西班牙的 13 家学术或教学医院进行。符合条件的参与者是 18 岁或以上的成年克罗恩病患者，他们接受了回肠结肠切除术并有一个或多个复发的危险因素。患者在手术后 4 周内 （比例为 1：1） 被随机分配在第 0 、 8 、 16 和 24 周接受静脉注射维得利珠单抗 （300 mg） 或安慰剂。使用计算机生成的经过验证的可变块模型集中进行随机化，并根据疾病行为（纤维狭窄 vs 炎症或穿孔）对患者进行分层。第 26 周进行回肠结肠镜检查并录像。内窥镜复发采用改良的 Rutgeerts 评分集中评估，分类评分范围为 i0 至 i4。主要终点是第 26 周时改良 Rutgeerts 评分在治疗组之间的分布，通过非参数方法进行分析。排名第一的次要终点是第 26 周时克罗恩病严重内窥镜复发的患者比例 （改良 Rutgeerts 评分 ≥i2b）。主要和安全性分析包括所有接受随机分组并接受至少一剂研究药物的患者。该试验已在欧盟临床试验注册库 （EudraCT;2015-000555-24） 注册。

 发现

在 2017 年 5 月 16 日至 2022 年 4 月 8 日期间，84 名患者被随机分配接受治疗，其中 4 名患者未接受研究治疗，维得利珠单抗组 43 名患者，安慰剂组 37 名患者。在第 26 周时，与安慰剂相比，维多珠单抗组改良 Rutgeerts 评分较低的概率为 77·8%（95% CI 66·4 至 86·3;p<0·0001）。维多珠单抗组 43 例患者中有 10 例 （23·3%） 观察到严重内窥镜复发，而安慰剂组 37 例患者中有 23 例 （62·2%） 发生严重内窥镜复发（差异 -38·9% [95% CI -56·0 至 -17·3];p=0·0004）。接受维得利珠单抗治疗的 43 名患者中有 3 名 （7·0%） 发生严重不良事件 （双侧输卵管卵巢脓肿、血栓性痔疮和胰腺癌） 和接受安慰剂的 37 名患者中有 2 名 （5·4%） 发生严重不良事件 （与克罗恩病和严重腹痛有关的肠穿孔）。

 解释

回结肠切除术后 4 周内接受维多珠单抗治疗比安慰剂更可能预防内窥镜下克罗恩病复发，使其成为有复发危险因素的患者术后管理的有吸引力的选择。需要更大规模的研究和更长的随访时间。

 资金

Takeda Nederland.