Medically reviewed by Onikepe Adegbola, MD, PhD
Crohn’s disease is an inflammatory bowel disease (IBD). It is the most difficult sickness to cure so far. In 10% of individuals, perianal fistulization is the initial symptom of Crohn’s disease.
For individuals with fistulizing CD, the ENTERPRISE trial assessed two vedolizumab intravenous dose regimens. Vedolizumab is a monoclonal antibody shown to be a safe and effective Crohn’s disease therapy. It also works to treat ulcerative colitis.
In patients with perianal fistulizing CD, intravenous (IV) doses of vedolizumab 300 mg enhanced fistulae response and perianal disease activity at week 30 according to research published in Clinical Gastroenterology and Hepatology.
ENTERPRISE is a global phase 4 research that looked at two different vedolizumab IV dose regimens for individuals with fistulizing CD. They had 1 to 3 perianal draining fistulas that had been present for 2 weeks before enrollment, and they had been diagnosed with moderate to severe CD 3 months before enrollment.
How did they design this study?
At weeks 0, 2, 6, 14, and 22, researchers gave 300 mg of intravenous vedolizumab to participants at random (the VDZ regimen). At week 10, they added a second dosage (the VDZ+wk10 regimen).
Those with moderate to severe CD with 1–3 active perianal fistulas were given 300 mg vedolizumab intravenously at weeks 0, 2, 6, 14, and 22 (VDZ) or the same regimen plus an extra dose at week 10 (VDZ + wk10).
Effects of Intravenous Vedolizumab
Vedolizumab was used to treat more than half of the patients with fistulizing CD in this research. They reported a 50% reduction in the number of draining perianal fistulae on clinical examination. Although the dose regimes were different, clinically significant decreases in draining fistulas were seen as early as week 2 and lasted until week 30.
However, there was one flaw in this research. Due to the lack of a placebo or seton plus antibiotic arm, the incidence of fistulae closure without vedolizumab therapy could not be assessed.
However, individuals with fistulizing CD who were given vedolizumab maintenance medication had a greater likelihood of closing their fistulas by 52 weeks than those who were given the placebo.
Limitations of the Study
Because of the small number of patients in each group and the likelihood of outliers, there were no conclusive responses about the effect of vedolizumab concentration on fistulae closure in this research. However, they did find that both IV vedolizumab regimens resulted in a persistent improvement in fistulae response from weeks 2 to 30.
Both vedolizumab IV 300 mg regimens showed improved fistula response and decreased perianal disease activity. An extra IV dosage of vedolizumab was not shown to enhance outcomes any more than the normal dose at week 10. Because the current therapy for CD is so difficult, more studies on intravenous vedolizumab might lead to better treatment.
The small research population resulting from the early enrollment closure restricts the generalizability of the findings of this study. As a result, more research with bigger sample sizes is required.
David A.Schwartz, Lauren. Biroule, Karen Lasch, Shashi Adsul, Silvio Danese (2021). Efficacy and Safety of 2 Vedolizumab Intravenous Regimens for Perianal Fistulizing Crohn’s Disease. Journal of Clinical Gastroenterology and Hepatology, 20(5), 1059-1067 https://doi.org/10.1016/j.cgh.2021.09.028