Endoscopic, Radiologic, and Histologic Healing With Vedolizumab in Patients With Active Crohn’s Disease

Abstract

BACKGROUND & AIMS: Vedolizumab is a gut-selective monoclonal antibody for the treatment of moderately to severely active Crohn's disease (CD). We performed a prospective study of endoscopic, radiologic, and histologic healing in patients with CD who received vedolizumab therapy. METHODS: We performed a phase 3b, open-label, single-group study of 101 patients with at least 3 months of active CD (a CD Activity Index [CDAI] score of 220-450, a simple endoscopic score for CD [SES-CD] of 7 or more, 1 or more mucosal ulcerations [identified by endoscopy], and failure of conventional therapy) from March 2015 through December 2017. Among the patients enrolled, 54.5% had previous failure of 1 or more tumor necrosis factor (TNF) antagonists and 44.6% had severe endoscopic disease activity (SES-CD scores above 15) at baseline. Participants received vedolizumab (300 mg intravenously) at weeks 0, 2, and 6, and then every 8 weeks thereafter, for 26 weeks (primary study) or 52 weeks (substudy, 56 patients). The primary endpoint at week 26 was endoscopic remission (SES-CD score of 4 or less); other endpoints included endoscopic response (50% reduction in SES-CD), radiologic remission (magnetic resonance index of activity score below 7), and histologic response (modified global histologic disease activity score of 4 or less). RESULTS: At week 26, 11.9% of patients were in endoscopic remission (95% confidence interval [CI] 6.3-9.8); at week 52, 17.9% of the patients were in endoscopic remission (95% CI 8.9-30.4). Higher proportions of patients naïve to TNF antagonists achieved endoscopic remission than patients with TNF-antagonist-failure at weeks 26 and 52. Higher proportion of patients with moderate CD (SES-CD scores, 7-15) achieved endoscopic remission at weeks 26 and 52 than patients with severe CD (SES-CD scores above 15). The proportion of patients with complete mucosal healing increased over time, with greater rates of healing in the colon than in the ileum. Remission was detected by magnetic resonance enterography in 21.9% of patients at week 26 (95% CI 9.3-40.0) and in 38.1% at week 52 (95% CI 18.1-61.6). At week 26, 24.4% of patients had a histologic response in the colon (95% CI 15.3-35.4) and 28.3% of patients had a histologic response in the ileum (95% CI 17.5-41.4). At week 52, 20.5% of patients had a histologic response in the colon (95% CI 9.8-35.3) and 34.3% of patients had a histologic response in the ileum (95% CI 19.1-52.2). There were no notable safety issues, including worsening of extraintestinal manifestations. CONCLUSIONS: In a phase 3b trial, we found that 26 and 52 weeks of treatment with vedolizumab (300 mg, at weeks 0, 2, and 6, and then every 8 weeks thereafter) induces endoscopic, radiologic, and histologic healing in patients with moderately to severely active CD. ClinicalTrials.gov no: NCT02425111.

A clinical decision support tool may help to optimise vedolizumab therapy in Crohn’s disease

“…Multiple studies in patients with active CD have shown a correlation between VDZ exposure and response, and higher clinical and endoscopic remission rates when stratified by drug exposure. [4][5][6][7][8][9][10] These findings hold out the possibility that dose intensification in patients with low VDZ trough concentrations during induction may result in higher remission rates. In support of this notion, observational data suggest that empiric administration of an additional drug dose in patients with suboptimal response to induction may improve outcomes.…”

“…Multiple studies in patients with active CD have shown a correlation between VDZ exposure and response, and higher clinical and endoscopic remission rates when stratified by drug exposure . These findings hold out the possibility that dose intensification in patients with low VDZ trough concentrations during induction may result in higher remission rates.…”

Effects of vedolizumab in Japanese patients with Crohn’s disease: a prospective, multicenter, randomized, placebo-controlled Phase 3 trial with exploratory analyses

“…Therefore, there was a possibility to interfere the data of efficacy by fewer patients of colonic type in the vedolizumab group. Two recent prospective trials have reported that endoscopic efficacy of vedolizumab for the ileum was inferior to that for the colon [19,20]. However, these trials were assessed by conventional ileocolonoscopy, and there is a possibility that proximal ileal lesions can be missed with this technique [21,22].…”

Predicting Response to Vedolizumab in Inflammatory Bowel Disease

“…Endoscopic response is an important part of disease assessment and is becoming a larger part of the treatment target in IBD. The recent VERSIFY phase 3b clinical trial (26) assessed endoscopic response to VDZ in CD and found that endoscopic remission rates (SES-CD score ≤ 4) were greater in patients naïve to TNF antagonists, those with moderate compared to severe baseline endoscopic disease, and shorter disease duration (26). Endoscopic remission rates at week 26 and 52 were higher in TNF-antagonist naïve (9.6 and 25%) vs. TNF-antagonist exposure (5.5 and 8.3%), higher in moderate disease (SES-CD 7-15) (17 and 20.7%) vs. severe disease (SES-CD > 15) (6.7 and 14.8%), and higher in shorter disease duration (<1 year) (37.5 and 100%) vs. longer disease duration (≥7 years) (7.1 and 11.5%).…”