Y-ECCO Literature Review: Gülden Bilican
Gülden Bilican
Vedolizumab to prevent postoperative recurrence of Crohn’s disease (REPREVIO): a multicentre, double-blind, randomised, placebo-controlled trial
D'Haens G, Taxonera C, Lopez-Sanroman A, et al.
Lancet Gastroenterol Hepatol 2025;10:26–33; DOI: 10.1016/S2468-1253(24)00317-0
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Introduction
Postoperative recurrence (POR) in Crohn’s Disease (CD) remains a significant clinical challenge. Surgical resection is often necessary to manage complications such as strictures, fistulas and abscesses, and disease recurrence is common in many patients without prophylactic treatment. Despite advances in surgical and medical management, recurrence rates remain alarmingly high. Endoscopic recurrence can occur in up to 90% of patients within one year of ileocolonic resection if left untreated , while clinical recurrence, typically defined in clinical trials using the Crohn’s Disease Activity Index (CDAI), occurs in up to 40% of patients within 12 months of surgery [1]. These rates underscore the importance of developing effective strategies to prevent disease recurrence and enhance long-term patient outcome. Ileocolonoscopy is the gold standard for diagnosing postoperative recurrence, as it defines the presence and severity of morphological recurrence. Both European and American guidelines recommend endoscopic monitoring within 6–12 months after surgery to evaluate for POR and guide treatment decisions, regardless of pharmacological prophylaxis [2, 3].
Current guidelines suggest using clincial predictors of early postoperative recurrence after ileocolonic resection to guide treatment. These potential predictors include smoking status, prior intestinal surgery, absence of prophylactic treatment, penetrating disease at index surgery, perianal location, granulomas in the resection specimen and myenteric plexitis. For patients with at least one of these risk factors, prophylactic treatment is strongly advised, with thiopurines or anti-TNFs historically being used as the preferred options to reduce the risk of recurrence [2]. Vedolizumab, a gut-selective integrin antagonist, has emerged as a promising alternative. D’Haens and colleagues conducted the first placebo-controlled clinical trial to date to assess the efficacy and safety of vedolizumab in reducing both the incidence and the severity of POR in patients with CD.
Methods
The REPREVIO trial was a multicentre, investigator-initiated study evaluating vedolizumab’s efficacy and safety in preventing POR of CD across 13 hospitals in France, Italy, the Netherlands and Spain. This double-blind, randomised, placebo-controlled trial followed patients over 26 weeks after ileocolonic resection with anastomosis. High-risk patients were included based on factors like prior surgery, TNF antagonist use, penetrating disease and smoking history. Participants were randomised within four weeks post-surgery to receive intravenous vedolizumab (300 mg) or placebo at weeks 0, 8, 16 and 24. At week 26, ileocolonoscopy, including a neoterminal ileal biopsy taken from the edges of ulcers, was conducted and video-documented. The primary endpoint was endoscopic recurrence, assessed via a modified Rutgeerts score at week 26 . Secondary endpoints included histopathological recurrence, clinical recurrence and adverse event rates.
The original statistical analysis intended to analyse severity of endoscopic recurrence as a dichotomous proportion. However, due to emerging statistical insights during the trial, the primary endpoint was analysed using a non-parametric approach (win probability) to estimate the probability that patients treated with vedolizumab would have lower endoscopic severity scores compared to patients treated with placebo.
Key findings
Ninety-five patients were screened, of whom 84 were randomly assigned to either vedolizumab or placebo. Of these, a total of 76 patients completed the REPREVIO trial, with 41 patients in the vedolizumab group and 35 in the placebo group.
The probability of a lower modified Rutgeerts score in vedolizumab-treated participants compared with placebo was 77.8% (p<0.0001). At week 26, severe endoscopic recurrence (modified Rutgeerts score ≥i2b) was observed in 10 of 43 patients (23.3%) in the vedolizumab group compared to 23 of 37 patients (62.2%) in the placebo group (p=0.0004). Overall endoscopic recurrence (>i0) occurred in 25 of 43 patients (58.1%) in the vedolizumab group versus 36 of 37 patients (97.3%) in the placebo group (p<0.0001).
Perhaps unsurprisingly, because the primary endpoint was at 6 months, clinical recurrence rates were similar between the groups, with clinical recurrence being observed in 9 of 43 patients (20.9%) in the vedolizumab group and 8 of 37 patients (21.6%) in the placebo group (p=0.94). It may, however, be more surprising that despite endoscopic differences, the percentage of patients with normal faecal calprotectin levels during follow-up was similar in the vedolizumab and placebo groups. There were no substantial differences in quality-of-life scores between the groups at 6 months. Adverse event rates were broadly similar between the placebo and vedolizumab arms, the main difference being in the reporting of flare or worsening of CD in the placebo arm.
Discussion
Vedolizumab demonstrated efficacy in reducing severe and overall endoscopic recurrence rates at week 26 compared to placebo, underscoring its role in preventing postoperative CD recurrence. Vedolizumab showed a reliable safety profile, consistent with earlier studies.
REPREVIO provides a welcome evidence base for a non-anti-TNF medication in the setting of POR. This could be particularly helpful for patients who have not responded, have lost response or have intolerance/contraindication to an anti-TNF.
Most previous studies on the prevention of POR have focused predominantly on the evaluation of anti-TNF agents, such as infliximab. The PREVENT trial demonstrated infliximab's efficacy in reducing endoscopic recurrence but did not meet its primary endpoint of preventing symptomatic recurrence at 18 months [4]. Macaluso et al. recently investigated the use of vedolizumab for the treatment (not prevention) of POR in 58 CD patients with endoscopic recurrence detected 6–12 months after ileocolonic resection. They found endoscopic benefit, defined as a reduction of at least one point in the Rutgeerts score, in 48% of patients, while 19% experienced clinical failure at one year. This study showed vedolizumab’s potential effectiveness not only in the prevention but also in the treatment of POR [5]. Combined with the REPREVIO trial, specifically assessing prevention of POR, these findings further support use of vedolizumab in postoperative CD.
Despite the strengths of this study, it is also important to consider some limitations. Notably, the trial had a relatively small sample size and a short follow-up period of only 6 months. As the authors highlight, larger studies with longer-term follow-up from vedolizumab use would be important for the future.
Conclusion
In summary, the REPREVIO trial represents an advance in the management of postoperative CD. By showing that vedolizumab reduces the rate and severity of endoscopic recurrence, D’Haens and colleagues demonstrate that it is a potentially effective prophylactic therapy for patients with CD at risk of postoperative recurrence.
References
- Regueiro M, Velayos F, Greer JB, et al. American Gastroenterological Association Institute Technical Review on the management of Crohn's disease after surgical resection. Gastroenterology 2017;152:277–95.e3. doi:10.1053/j.gastro.2016.10.03.
- Gionchetti P, Dignass A, Danese S, et al; on behalf of ECCO. 3rd European evidence-based consensus on the diagnosis and management of Crohn’s disease 2016: Part 2: Surgical management and special situations. J Crohns Colitis 2017;11:135–49. doi:10.1093/ecco-jcc/jjw169.
- Nguyen GC, Loftus EV Jr, Hirano I, et al. American Gastroenterological Association Institute guideline on the management of Crohn's disease after surgical resection. Gastroenterology 2017;152:271–5. doi:10.1053/j.gastro.2016.10.038.
- Regueiro M, Feagan BG, Zou B, et al. Infliximab reduces endoscopic, but not clinical, recurrence of Crohn's disease after ileocolonic resection. Gastroenterology 2016;150:1568–78. doi:10.1053/j.gastro.2016.02.072.
- Macaluso FS, Cappello M, Crispino F, et al. Vedolizumab may be an effective option for the treatment of postoperative recurrence of Crohn's disease. Dig Liver Dis 2022;54:629–34. doi:10.1016/j.dld.2021.11.021.
Profile
Gülden Bilican is a gastroenterology registrar currently in her third year of training at Gazi University Medical School Hospital in Ankara, Turkey. She has a special interest in intestinal ultrasound and the management of Inflammatory Bowel Diseases.