Vedolizumab Yields Positive Results for Patients with Crohn's Disease

Vedolizumab could help patients achieve endoscopic and histologic remission in a difficult to treat segment of patients with Crohn’s disease (CD).

A team of investigators, led by Mark Löwenberg, University of Amsterdam, evaluated the ability of vedolizumab to induce endoscopic and histologic remission for patients with Crohn’s disease in a 110-patient prospective study.

The study included patients with active Crohn’s disease, based on a CD activity index (CDAI) score greater than 220 and mucosal ulcerations, who received 300 mg of open-label vedolizumab infusions at weeks 0, 2, and 6, and every 8 weeks after through a 52-week program at tertiary centers in Belgium and the Netherlands.

Patients received an additional infusion at week 10 if their CDAI score did not decrease by 70 points and underwent an ileocolonoscopy with a collection of biopsies at baseline and at weeks 26 and 52, where a local and central reader determined simple endoscopic index for CD (SES-CD) scores.

The investigators assessed histologic features with a blinded pathologist at week 26 and serum concentrations of vedolizumab were measured at serial time points.

The primary outcome of the study was endoscopic and histologic remission in patients with active Crohn’s disease treated with vedolizumab for 52 weeks.

“At weeks 26 and 52, 36 patients (29%) and 34 patients (31%), respectively, were in corticosteroid-free clinical remission (CDAI score <150), respectively,” the authors wrote. “Based on intent-to-treat analysis, endoscopic remission (SES-CD score <4) was achieved by 36 patients (33%) and 40 patients (36%) at weeks 26 and 52.”

Endoscopic responses—decreases in SES-CD scores at least 50%--also occurred in 44 patients (40%) at week 26, as well as in 5 patients (45%) at week 52.

They ultimately found serum concentrations of vedolizumab were higher at weeks 2, 10, and 22 in patients with lower SES-CD scores.

The team observed histologic remission at week 26 in 43 (64%) of 67 patients based on Geboses Score and 37 (66%) of 56 patients based on Robarts Histopathology Index scores in an analysis of paired biopsies with inflammation at baseline.

Serum concentrations of vedolizumab above 10 mg/L at week 22 were associated with endoscopic remission at week 26.

“In a prospective trial, we found that approximately one-third of patients with CD achieve endoscopic remission after 52 weeks of treatment with vedolizumab and two-thirds achieve histologic remission at week 26,” the authors wrote. “Higher serum concentrations of vedolizumab were associated with better outcomes.”

Vedolizumab is a gut-selective humanized monoclonal antibody that binds to the α4β7 integrin to inhibit leucocyte vascular adhesion and migration into the gastrointestinal mucosa.

Currently, the drug is approved to treat moderate to severe Crohn’s disease, based on the results of the GEMINI 2 and 3 phase 3 randomized controlled trials. While the efficacy and safety of vedolizumab induction and maintenance therapy has been confirmed in cohort trials, only limited data is available on endoscopic and histological remission.

The study, “Vedolizumab Induces Endoscopic and Histologic Remission in Patients With Crohn’s Disease,” was published online in Gastroenterology.