D'Haens Geert, Taxonera Carlos, Lopez-Sanroman Antonio, Nos Pilar, Danese Silvio, Armuzzi Alessandro, Roblin Xavier, Peyrin-Biroulet Laurent, West Rachel, Mares Wout G N, Duijvestein Marjolijn, Gecse Krisztina B, Feagan Brian G, Zou Guangyong, Hulshoff Melanie S, Mookhoek Aart, Oldenburg Lotte, Clasquin Esmé, Bouhnik Yoram, Laharie David
Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Amsterdam, Netherlands.
Hospital Clinico San Carlos, Madrid, Spain.
Lancet Gastroenterol Hepatol. 2025 Jan;10(1):26-33. doi: 10.1016/S2468-1253(24)00317-0. Epub 2024 Nov 18.
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.
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).
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).
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.
Takeda Nederland.
约半数克罗恩病患者需要进行回结肠切除术。其中，50%的患者随后会在1年内出现内镜下疾病复发。我们旨在评估维多珠单抗预防克罗恩病术后复发的疗效和安全性。
REPREVIO是一项在法国、意大利、荷兰和西班牙的13家学术或教学医院进行的双盲、随机、安慰剂对照试验。符合条件的参与者为年龄在18岁及以上、患有克罗恩病且接受了回结肠切除术并有一个或多个复发风险因素的成年患者。患者在手术后4周内（1:1比例）被随机分配，在第0、8、16和24周接受静脉注射维多珠单抗（300毫克）或安慰剂。随机分组通过计算机生成的经过验证的可变区组模型集中进行，患者根据疾病行为（纤维狭窄型与炎症型或穿孔型）进行分层。在第26周进行回结肠镜检查并录像。内镜复发情况通过改良的 Rutgeerts 评分进行集中评估，这是一个从i0到i4的分类评分。主要终点是第26周时治疗组之间改良Rutgeerts评分的分布情况，采用非参数方法进行分析。首要的次要终点是第26周时克罗恩病严重内镜复发患者的比例（改良Rutgeerts评分≥i2b）。主要分析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。
在2017年5月16日至2022年4月8日期间，84例患者被随机分配接受治疗，其中4例未接受研究治疗，最终维多珠单抗组有43例患者，安慰剂组有37例患者。在第26周时，与安慰剂相比，维多珠单抗使改良Rutgeerts评分降低的概率为77.8%（95%置信区间66.4%至86.3%；p<0.0001）。维多珠单抗组43例患者中有10例（23.3%）出现严重内镜复发，而安慰剂组37例患者中有23例（62.2%）出现严重内镜复发（差异 -38.9% [95%置信区间 -56.0%至 -17.3%]；p = 0.0004）。接受维多珠单抗治疗的43例患者中有3例（7.0%）发生严重不良事件（双侧输卵管卵巢脓肿、血栓性痔疮和胰腺腺癌），接受安慰剂治疗的37例患者中有2例（5.4%）发生严重不良事件（与克罗恩病相关的肠穿孔和严重腹痛）。
回结肠切除术后4周内使用维多珠单抗比安慰剂更有可能预防内镜下克罗恩病复发，这使其成为有复发风险因素患者术后管理的一个有吸引力的选择。需要进行更大规模、随访时间更长的研究。
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