Clin Gastroenterol Hepatol. 2022 May;20(5):1059-1067.e9.doi: 10.1016/j.cgh.2021.09.028. Epub 2021 Sep 29.

David A Schwartz ¹, Laurent Peyrin-Biroulet ², Karen Lasch ³, Shashi Adsul ⁴, Silvio Danese ⁵

Author information

¹Inflammatory Bowel Disease Center, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address: david.a.schwartz@vanderbilt.edu.

²Department of Gastroenterology, Nancy University Hospital, Nancy, France; Inserm U1256 NGERE, Lorraine University, Nancy, France.

³Takeda Pharmaceuticals USA Inc, Lexington, Massachusetts.

⁴Takeda Pharmaceuticals International AG, Zurich, Switzerland.

⁵IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milano, Italy.

Abstract

Background & aims: Fistulizing Crohn's disease (CD) is challenging to treat. We report results from ENTERPRISE, a randomized, double-blind, phase 4 trial evaluating 2 vedolizumab intravenous dosing regimens in patients with fistulizing CD.

Methods: Patients with moderately to severely active CD and 1-3 active perianal fistulae (identified on magnetic resonance imaging [MRI]) received vedolizumab 300 mg intravenously at weeks 0, 2, 6, 14, and 22 (VDZ) or the same regimen plus an additional vedolizumab dose at week 10 (VDZ + wk10). Reduction from baseline in draining perianal fistulae and disease activity, MRI assessments, health-related quality of life (HRQoL), and safety were evaluated. Enrollment was stopped prematurely because of recruitment challenges; analyses are descriptive.

Results: Of 32 patients with ≥1 active fistulae at baseline per MRI and postbaseline fistulae healing assessment, 28 (14 per dosing regimen) had ≥1 draining fistulae at baseline (assessed by gentle finger compression during clinical exam). Rapid and sustained fistula closure was observed; 53.6% (VDZ, 64.3%; VDZ + wk10, 42.9%) and 42.9% (VDZ, 50.0%; VDZ + wk10, 35.7%) of patients achieved ≥50% decrease in draining fistulae and 100% fistulae closure, respectively, at week 30. Mean (standard deviation) CD and Perianal Disease Activity Index scores decreased by 51.1 (78.3) and 4.1 (3.3), respectively, at week 30. HRQoL improved throughout the study. No new safety signals were observed.

Conclusions: Sustained improvements in fistulizing CD were seen with both vedolizumab regimens. An additional dose at week 10 does not appear to alter treatment outcomes. Safety profile was consistent with other vedolizumab studies.

Clinicaltrials: gov no: NCT02630966; EudraCT: 2015-000852-12.