VEDOLIZUMAB PREVENTS POSTOPERATIVE REUCURRENCE IN CROHN’S DISEASE: RESULTS OF THE REPREVIO TRIAL

Background: Crohn’s disease (CD) is a chronic inflammatory intestinal disorder, for which the majority of patients need to undergo surgery. Following ileocolonic resection, most patients experience recurrent CD in the neoterminal ileum. Endoscopic lesions usually precede symptoms and predict the severity of the disease course. No treatments have been approved for recurrence-prevention CD. REPREVIO is a prospective placebo-controlled randomized trial investigating the preventive effect of vedolizumab, an anti-integrin antibody, on recurrence of CD.
Methods: Following ileocolonic resection, patients were randomized to treatment with intravenous vedolizumab (300 mg at week 0,8,16 and 24) or PLC (1:1) at 12 sites in the Netherlands, France, Italy and Spain. Patients and investigators were blinded to treatment assignment that was initiated within 4 weeks of ileocolonic resection with anastomosis. Twenty-six weeks after randomization patients underwent ileocolonoscopy for assessment of recurrent CD lesions. Video recordings were centrally scored using the modified Rutgeerts’ score (i0-i4) by 2 readers with adjudication in case of disagreement. The primary endpoint was endoscopic recurrence (ER) of Crohn’s disease according to Rutgeerts classification categories (non-parametric analysis of distributions between groups); secondary endpoints were the proportion of patients with ER >i2a, endoscopic remission (i0) and clinical recurrence (CDAI increase >70 points between baseline and week 24). Data analysis was based on intent-to-treat with patients dropping out or not having final endoscopy counted as failure (i4). Adverse events were recorded.
Results: Of 95 pts screened, 80 were randomized. Seventy-six patients reached week 26 (2 drop-outs for withdrawal of consent, 1 for perforation and 1 for cancer). Baseline patient characteristics were comparable as shown in table 1. Using a non-parametric analysis, patients in the treatment group had a 77.8% (95% CI 66.4 to 86.29%) chance of having a better Rutgeerts’ score than control patients (p <0.0001). Based upon the dichotomized analysis of high risk recurrence versus low risk recurrence (i0-2A versus i2B-i4), 77% of patients who received VDZ had i0-2A versus 38% for PLC, yielding an absolute difference of 39% in favor of VDZ (p=0.0004)(figure 1). Endoscopic remission (i0) was observed in 18/43 pts for VDZ (42%) versus 1/37 pt for PLC (3%)(p<0.001). Clinical recurrence (CDAI increase >70 pts between baseline and week 24) occurred in 9 pts on VDZ and 8 pts on PLC. No new safety signals were observed.
Conclusion: Treatment with VDZ started immediately after ileocolonic resection is highly effective for the prevention of postoperative recurrence of CD.