Vedolizumab to prevent postoperative recurrence of Crohn's disease (REPREVIO): a multicentre, double-blind, randomised, placebo-controlled trial

Abstract

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.