Vedolizumab prevents postop CD recurrence: new indication likely

Patients with resected Crohn’s disease (CD) who were treated with the gut-selective α4β7-integrin inhibitor vedolizumab were less likely to have endoscopic signs of recurrence compared with placebo in the Reprevio study presented at DDW 2023.

“Of 43 patients treated with vedolizumab, 18 had no CD-like lesions after 6 months vs one in 37 with placebo,” reported Dr Geert D’Haens, professor of gastroenterology at the Amsterdam University Medical Center in the Netherlands.

Recurrence after resection

Eleven patients on placebo had an i4 rating in the Rutgeerts score compared with 3 in those treated with vedolizumab. The Rutgeers score has 5 grades of severity (i0 –i4, with 0 meaning absence of endoscopic lesions). An i4 rating suggests diffuse ileal inflammation with ulcers, nodules and/or stenosis.

“Overall, patients treated with vedolizumab had a 78 percent probability of getting a lower Rutgeers score vs those on placebo,” D’Haens said. The trial met its primary endpoint. Safety findings were consistent with those previously reported for vedolizumab. [DDW 2023, abstract 603]

Patients have unmet medical needs

Patients with CD have chronic, relapsing intestinal inflammation. The goal of treatment is to induce remission and prevent a relapse. Despite drug therapy, many patients still require ileocecal resection. However, recurrence after resection is common.

“Currently, there is no therapy approved to prevent recurrence. Patients have a significant unmet need,” emphasized D’Haens. “As lymphocyte trafficking is inhibited by vedolizumab, we hypothesized this drug could prevent postop recurrence.”

Eighty patients were randomly assigned to vedolizumab 300 mg, infused every 8 weeks, starting within 4 weeks of surgery, or placebo. Colonoscopies were performed after 6 months.

Eligibility was decided based on the presence of one risk factor which can be active smoking, previous bowel resections, surgery for abscess or fistula, or previous use of tumour necrosis factor inhibitors (TNFi) that were discontinued 6 weeks prior to screening.

The mean age of the patients was 36 years. Over half of them were men. CD duration was about 9 years.

Serious adverse effects were uncommon. There was no difference in symptom recurrence between groups (22 percent with placebo and 21 percent with vedolizumab).

Clinical outcomes should not be ignored

A DDW attendee commented that recurrence may not be “a meaningful outcome in a rigorous clinical trial setting,” to which session co-moderator Dr Paul Moayyedi from McMaster University in Hamilton, Ontario, defended: “It’s a disservice to our patients to ignore clinical outcomes in treatment trials.”

Where to next for vedolizumab?

Vedolizumab is approved in major markets for the treatment of both moderate-to-severe CD and ulcerative colitis.