P476 Efficacy and safety of 2 vedolizumab IV regimens in patients with perianal fistulising Crohn’s disease: results of the ENTERPRISE study

Abstract

Abstract Background Perianal fistulae occurring with Crohn’s disease (CD) are a challenge to treat. Vedolizumab (VDZ) is a gut-selective, monoclonal α 4β7 integrin antibody approved to treat patients (patients) with moderately to severely active CD. Here we report results from ENTERPRISE (NCT02630966; EudraCT 2015-000852-12), a randomised, double-blind, phase 4 trial to evaluate 2 VDZ IV dosing regimens in patients with fistulising CD. Methods Patients with moderately to severely active CD and 1–3 draining perianal fistulae received either VDZ 300 mg IV at Weeks (Week) 0, 2, 6, 14, and 22 (VDZ), or the same regimen plus an additional VDZ dose at Wk10 (VDZ+Wk10). The primary endpoint was the proportion of patients with a ≥50% reduction from baseline (BL) in the number of draining fistulae (absence of draining despite gentle finger compression) at Wk30. Secondary endpoints were the proportion of patients with a ≥50% reduction from BL in the number of draining fistulae at Wk22 and Wk30, and the proportion of patients with 100% fistulae closure at Wk30. Patients with missing data at study visits were counted as non-responders. Perianal disease activity index (PDAI), perianal pain score, Van Assche score, gadolinium contrast enhancement by pelvic MRI, and safety were assessed. Study enrolment closed early due to slow recruitment; thus, all analyses are descriptive. Results Of the 32 patients with post-BL assessment of fistulae healing (full analysis set, FAS), 28 had ≥1 draining fistula at BL (modified FAS). Median CD duration was 8.5 years (VDZ [n = 14]: 11.2 years; VDZ+ Week 10 [n = 14]: 6.1 years). In each arm, 11 patients (78.6%) had prior anti-tumour necrosis factor therapy at BL; concomitant corticosteroid use was 21.4% (VDZ) and 14.3% (VDZ+ Week 10), and concomitant immunosuppressant use was 28.6% (VDZ) and 21.4% (VDZ+ Week 10). At Wk30, 53.6% of all patients achieved ≥50% decrease in the number of draining fistulae (VDZ: 64.3%; VDZ+ Week 10: 42.9%; Figure 1). The proportion of patients with fistulae response increased rapidly and remained high through Week 30 (Figure 2); 46.4% of patients (VDZ: 57.1%; VDZ+Week 10: 35.7%) achieved ≥50% decrease in the number of draining fistulae at both Weeks 22 and 30. Closure of all fistulae draining at BL was observed at Week 30 in 42.9% of patients (VDZ: 50.0%; VDZ+ Week 10: 35.7%). In the FAS, mean (SD) PDAI scores changed from BL to Weeks 30–4.1 (3.3) and perianal pain scores changed –2.2 (2.7) (table). At Wk30, mean (SD) Van Assche scores and contrast enhancement scores changed –1.1 (3.1) and –9.5 (69.4) from screening, respectively. No new safety signals were observed. Conclusion Over half of CD patients treated with VDZ had reductions of ≥50% in the number of draining perianal fistulae. Clinically relevant reductions in draining fistulae were seen as early as Wk2 and maintained through Wk30.