Intravenous (IV) regimens of vedolizumab 300 mg were associated with improvements in fistulae response and perianal disease activity at week 30 in patients with perianal fistulizing Crohn disease (CD), according to a study in Clinical Gastroenterology and Hepatology.

Researchers presented results from ENTERPRISE, a multinational, phase 4 trial investigating 2 vedolizumab IV dosing regimens in patients with fistulizing CD. Patients were diagnosed with moderate to severe CD ≥3 months before enrollment and had 1 to 3 perianal draining fistulae ongoing for ≥2 weeks before enrollment.

The patients were randomly assigned 1:1 to receive 300 mg IV vedolizumab at weeks 0, 2, 6, 14, and 22 (VDZ regimen), or the same regimen with an additional vedolizumab dose at week 10 (VDZ+wk10).


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The primary endpoint was a ≥50% decrease from baseline in the number of draining perianal fistulae at week 30, in which closed fistulae were no longer draining, despite gentle finger compression.

A total of 34 patients were randomly assigned (VDZ, n = 16; VDZ+wk10, n = 18) and received ≥1 dose of vedolizumab (safety/pharmacokinetic set). Of this group, 32 participants (VDZ, n = 16; VDZ+wk10, n = 16) had a postbaseline evaluation (full analysis set [FAS]), of which 28 patients (median age, 34.0 years; 60.7% men) had ≥1 draining fistula at baseline. Overall, 24 patients completed treatment, and 10 prematurely discontinued treatment.

At week 30, 15 (53.6%) of 28 modified FAS (mFAS) patients achieved the primary endpoint, as assessed in the clinical examination (VDZ, n = 9 [64.3%]; VDZ+wk10, n = 6 [42.9%]).

In addition, 13 patients (46.4%) had a ≥50% decrease in the number of draining fistulae at weeks 22 and 30 (VDZ, n = 8 [57.1%]; VDZ+wk10, n = 5 [35.7%]); 100% closure of fistulae draining at week 30 occurred in 12 (42.9%) patients (VDZ, n = 7 [50.0%]; VDZ+wk10, n = 5 [35.7%]).

Mean Crohn Disease Activity Index scores decreased by 52.8 (SD, 75.8) points, Perianal Disease Activity Index scores decreased by 3.9 (SD, 3.3) points, and perianal pain score was reduced by 2.2 (SD, 2.3) points at week 30.

Improvement was also observed in health-related quality of life. The mean baseline value for total inflammatory bowel disease questionnaire score was 137.6 (SD, 36.9), and the mean change from baseline to week 30 was 25.5 (SD, 22.1) among mFAS patients. Scores on the Euro Quality of Life-5 Dimensions (index and visual analog scale) also increased from baseline to week 30.

Adverse events (AEs) were reported in 32 patients (94.1%), and 13 (38.2%) had a treatment-related AE. Most AEs were mild to moderate in severity. Serious adverse events occurred in 7 patients (20.6%), and 4 patients (11.8%) discontinued treatment due to AEs.

The investigators noted that their study is limited by the lack of placebo and/or seton plus antibiotic arm.

“Overall, these results suggest vedolizumab IV may be beneficial in treating patients with fistulizing CD,” stated the researchers.

Disclosure: This study was sponsored by Takeda. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Schwartz DA, Peyrin-Biroulet L, Lasch K, Adsul S, Danese S. Efficacy and safety of 2 vedolizumab intravenous regimens for perianal fistulizing Crohn’s disease: ENTERPRISE study. Clin Gastroenterol Hepatol. Published online September 29, 2021. doi: 10.1016/j.cgh.2021.09.028