Mucosal healing (MH) is an important treatment goal for inflammatory bowel disease (IBD). Vedolizumab (VDZ), a gut-selective anti-lymphocyte trafficking agent, has shown potential to achieve MH. EARNEST, a randomized double-blind placebo-controlled trial of VDZ in chronic pouchitis, offers a robust dataset systematically collected from the inflamed pouch mucosa to further explore the impact of VDZ treatment on MH.
EARNEST evaluated intravenous VDZ (300 mg) vs placebo (PBO) administered at weeks 0, 2, 6, 14, 22, and 30, in adult patients (pts) with active chronic pouchitis despite antibiotic therapy after proctocolectomy and ileal pouch-anal anastomosis for ulcerative colitis. Endoscopic imaging was captured and centrally read at baseline, Week (W) 14, and W34. Total ulceration and SES-CD (modified to apply to a single segment) were evaluated. Microscopic inflammation was also evaluated using the Pouchitis Disease Activity Index (PDAI) histological component. Pre-specified exploratory endpoints included changes in total ulceration and SES-CD remission (score ≤2); MH was defined post-hoc as SES-CD=0 plus PDAI histology score ≤1 (none/mild polymorphic nuclear leukocyte infiltration and no ulceration). Fecal calprotectin (FCP) levels were explored by MH status. PDAI remission (score <7 and ≥3 point-reduction from baseline) and Inflammatory Bowel Disease Questionnaire (IBDQ) remission (score ≥170) were assessed in pts with/without MH at W14.
In total, 98 pts had endoscopic evaluations (VDZ n=48; PBO n=50). Ulcers/erosions were higher in VDZ pts at baseline with a greater reduction at W14 and W34 with VDZ vs PBO. More pts treated with VDZ vs PBO achieved reduction in ulcerated surface area, complete absence of ulceration/erosions and SES-CD remission. At W14, 7/42 (16.7%) pts had MH on VDZ vs 1/40 (2.5%) on PBO. All 7 VDZ pts with MH at W14 were in PDAI remission at W14 and W34; 6/7 (85.7%) pts achieved IBDQ remission at W14 and 5/7 (71.4%) achieved IBDQ remission at both W14 and W34. Of the 35 VDZ-treated pts without MH at W14, 11/35 (31.4%) achieved PDAI remission at W14, 11/35 (31.4%) at W34, and 9/35 (25.7%) at both W14 and W34; 13/35 (37.1%) achieved IBDQ remission at W14, 17/35 (48.6%) at W34, and 12/35 (34.3%) at both W14 and W34. MH was associated with FCP ≤250 µg/g while ~40-60% of pts without MH had FCP >250 µg/g.
VDZ was associated with better control of markers of inflammation vs PBO, based upon improvements in endoscopic/histologic outcomes in the pouch mucosa, as well as improved outcomes reported by pts. These effects of VDZ in the pouch mucosa are consistent with those observed in the wider patient population with IBD.