Chief of the Digestive Disease Institute
Cleveland Clinic, Cleveland
One of my long-standing research interests is how to prevent endoscopic or symptomatic Crohn’s disease recurrence after surgical resection.
To investigate this question, in 2016, I led the PREVENT study, a randomized controlled trial exploring whether infliximab was effective at preventing endoscopic or clinical recurrence of CD in 287 patients up to 76 weeks after surgery. We found a significantly lower rate of endoscopic recurrence in people who received infliximab, as well as a reduction in symptomatic (clinical) recurrence, although this was not statistically significant.
While I believe PREVENT contributed to our field, the need to explore how to reduce postsurgical CD recurrence remains. The first study in this month’s report, REPREVIO, adds to our understanding. In this study, researchers compared vedolizumab (Entyvio, Takeda) with placebo and found a statistically lower rate of endoscopic recurrence in the vedolizumab arm after surgery.
The study included 80 participants who underwent surgery and were evaluated through week 26. The numbers are modest, but the trend line is clear. Although we’ll see whether the benefit continues beyond six months, vedolizumab appears to prevent postoperative CD.
It is gratifying to see emerging evidence that another biologic can lower CD recurrence after surgery.
The other study this month, an external validation of a previous clinical trial, shows that blood-based biomarkers can predict which patients with CD would be most likely to relapse after stopping infliximab.
It’s natural for someone to consider discontinuing a treatment after a long period of remission. Nobody wants to take a medication forever unless it is necessary. The problem is that we do not have a good way to know which patients can safely do this. This study, however, points the way toward that future. The authors show that several biomarkers can be useful guides of likely CD recurrence after discontinuation of infliximab.
We’re still a long way from incorporating this information into clinical practice. The biomarkers evaluated in this study are measured in research settings but are not yet available to use in our clinics.
That said, this study is an exciting demonstration of the potential of personalized medicine. And it’s very possible that this work, and other studies like it, will eventually guide clinical care and decision-making around de-escalation or cessation of specific therapies.
Vedolizumab to Prevent Postoperative Recurrence of Crohn’s Disease (REPREVIO)
Lancet Gastroenterol Hepatol 2025;10(1):26-33
Of 76 adults with CD who had an ileocolonic resection and were at risk for recurrence, 41 received 300 mg of IV vedolizumab and 35 were administered placebo. Participants in the vedolizumab arm received the medication at weeks 0, 8, 16 and 24, and all the patients had a subsequent colonoscopy to evaluate endoscopic recurrence.
At week 26, there was a significantly lower probability (77.8%) of endoscopic recurrence—measured by the modified Rutgeerts score—in the vedolizumab arm (95% CI, 66.4%-86.3%; P<0.0001). Those in the placebo arm were much more likely to have a Rutgeerts score higher than i2b.
Serum Biomarkers to Predict Relapse in Crohn’s Disease Patients Discontinuing Infliximab
Gut 2024;73:1965-1973
Researchers measured serum proteins using inflammatory response markers, immune response panels and cytokine panels in patients with CD who stopped taking infliximab. The goal was to see which biomarkers best predicted relapse risk.
Of 186 adults with CD who stopped taking infliximab, 31 relapsed within six months of infliximab withdrawal (defined as short-term relapse), with another 46 relapsing after six months and up to slightly more than a year after withdrawal (mid-/long-term relapse). For all participants, relapse was defined as a rise in the Clinical Disease Activity Index (CDAI) between 150 and 250, with a rise of more than 70 points over two visits one week apart, or a CDAI higher than 250.
Several blood proteins were predictive of relapse risk. Specifically, high levels of proteins linked to an inflammatory response, such as haptoglobin and C-type lectin domain family 4 member C, were associated with short-term relapse. Low levels of proteins with anti-inflammatory properties, such as kallistatin and fibroblast growth factor 2, were associated with mid- and long-term relapse.
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