BACKGROUND: Vedolizumab (VDZ) is a gut-selective monoclonal anti-α4β7-integrin antibody approved for the treatment of adult patients (pts) with moderately to severely active Crohn's disease (CD). Mucosal healing, an important therapeutic goal in CD, was not evaluated as an endpoint in pts with CD during the VDZ clinical development program. A systematic review and meta-analysis of published real-world studies was conducted to examine the rates of mucosal healing in VDZ-treated pts with CD.
METHODS: MEDLINE, Cochrane, and EMBASE-indexed publications from Jan, 2014 to Jan, 2020 and conference abstracts from 2018 and 2019 were searched for real-world studies reporting mucosal healing and related outcomes in VDZ-treated pts with CD. Reports with <10 pts and pts aged <18 years were excluded. A meta-analysis was conducted in R using meta to generate pooled estimates of mucosal healing. Primary analysis included studies reporting point estimates of mucosal healing/endoscopic remission as Simple Endoscopic Score for CD (SES-CD) using cut-points <4 or absence of ulcer and/or erosions at 6 months and 12 months. Secondary analysis was performed considering point estimates, cumulative rates, and data up to 12 months.
RESULTS: The review included 36 VDZ studies (22 reported mucosal healing; 9 endoscopic remission; 6 reported endoscopic response; and other outcomes were reported for the remaining studies). Median pt age ranged from 29.0-49.5 years, median disease duration 2.35-19.50 years. Rates of stricturing, penetrating, and perianal disease were 21.3-48.0%, 10.3-50.0%, and 12.0-46.0%, respectively; and prior use of anti-TNFα agents ranged from 62.2% to 99.4%. Most studies defined mucosal healing/endoscopic remission as absence of ulcers and/or erosions (17 studies) or SES-CD <4 (6 studies). Mucosal healing rates ranged from 10.1-46.0% at 6 months (11 studies) and 21.2-62.5% at 12 months (11 studies). Endoscopic remission rates ranged from 15-33% at 6 months and 27-36% at 12 months. Pooled rates of mucosal healing considering point estimates were ~31.8% at 6 months (N=223) (Figure 1) and 33.4% at 12 months (N=151) (Figure 2). In the secondary analysis, pooled rates of mucosal healing up to 12 months were 41.5% (N=1155, 12 studies). Mucosal healing rates were 54-62.5% in anti-TNFα naïve pts (3 studies) and 66.7% in pts with corticosteroid-free remission (1 study) at 12 months.
CONCLUSION: In real-world clinical settings, approximately one-third of VDZ-treated pts with CD achieved mucosal healing both at 6 months and at 12 months, despite utilization in largely biologic-refractory pts. These study findings support the effectiveness of VDZ for achieving mucosal healing in pts with CD.
