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OP023 A phase 3b open-label multicentre study (VERSIFY) of the efficacy of vedolizumab on endoscopic healing in moderately to severely active Crohn’s disease (CD)

S. Danese1*, B. Feagan2, W. Sandborn3, J.-F. Colombel4, S. Vermeire5, S. Jones6, K. Brennan6, J. Bornstein7

1Humanities University, IBD Center, Humanitas Clinical and Research Center, Rozzano, Milan, Italy, 2University of Western Ontario, Robarts Clinical Trials, London, Ontario, Canada, 3University of California, Inflammatory Bowel Disease Center, Division of Gastroenterology, San Diego, USA, 4Icahn School of Medicine at Mount Sinai, Department of Gastroenterology, New York, NY, USA, 5University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium, 6Europe Development Centre, Takeda R&D, London, UK, 7Takeda Pharmaceuticals International Co., Cambridge, MA, USA

Background

Vedolizumab (VDZ) is a gut-selective humanised immunoglobulin G1 monoclonal antibody that prevents the trafficking of T-lymphocytes into the gastrointestinal submucosa by antagonising the interaction of alpha4beta7 integrin with its ligand, mucosal addressin cell adhesion molecule 1 (MAdCAM-1).1 VDZ has demonstrated statistically significant differences in clinical remission from placebo in patients (patients) with moderately to severely active Crohn’s disease (CD),2 but endoscopic healing was not previously assessed. The present study evaluated the effect of VDZ on endoscopic remission and healing in patients with CD.

Methods

Patients with moderately to severely active CD (≥3 months; CD Activity Index [CDAI] 220-450; Simple Endoscopic Score for CD [SES-CD] ≥7; ≥1 mucosal ulceration on centrally read endoscopy) who had previously experienced treatment failure with corticosteroids, immunomodulators, and/or at least one tumour necrosis factor-alpha (TNF) antagonist were enrolled. Patients received VDZ 300 mg intravenously at weeks 0, 2, 6, and then every 8 weeks for 26 weeks, followed by a 26-week treatment extension period. The primary endpoint was endoscopic remission (SES-CD ≤4) at week 26, assessed by centrally read ileocolonoscopy. Key secondary endpoints included endoscopic response (SES-CD ≥50% reduction from baseline) and complete endoscopic healing (absence of ulcerations) at week 26. Subgroup analyses stratified by TNF antagonist exposure status were performed for all endpoints and by disease severity for endoscopic remission only.

Results

Of the 101 patients enrolled, 55% had previously failed at least one TNF antagonist (TNF-F), and 46% were categorised as having severe endoscopic activity at entry (SES-CD score of >15). Endoscopic remission rates at week 26 were 12% overall, 20% in TNF antagonist naïve (TNF-N), and 6% in TNF-F patients, respectively (Table 1). Endoscopic remission at week 26 was achieved in 17% of patients with moderate endoscopic activity (SES-CD score of 7–15) compared with 7% of patients with severe disease. Endoscopic response and complete endoscopic healing rates at week 26 are shown in Table 1.

Table 1. Endoscopic outcomes at week 26 by TNF antagonist status.

Conclusion

VDZ demonstrated the ability to induce endoscopic remission and healing in a refractory population. TNF-N patients were more likely to achieve endoscopic remission and healing than those with previous treatment failure to a TNF antagonist.

References

1.Soler D, et al. The binding specificity and selective antagonism of vedolizumab, an anti-α4β7 integrin therapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp Ther, 2009:330;864-–75, 330.

2.Sandborn WJ, et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med, 2013;369:711–21.