ENTERPRISE Study: Vedolizumab for Perianal Fistulizing Crohn’s Disease

DA Schwartz et al. Clin Gastroenterol Hepatol 2022; 20: 1059-1067. Open Access: Efficacy and Safety of 2 Vedolizumab Intravenous Regimens for Perianal Fistulizing Crohn’s Disease: ENTERPRISE Study

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)… Enrollment was stopped prematurely because of recruitment challenges”

Key findings:

  • “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”
  • “MRI healing, defined as the disappearance of T2 hyperintensity signal and absence of gadolinium contrast enhancement,3 was not reached in this study…gadolinium contrast enhancement showed improvement at week 30…MRI studies have shown that internal fistulae healing lags behind clinical remission by a median of 12 months”
Figure 1
Figure 2 B

The study findings are limited by relatively small size and lack of control group (eg. placebo or seton/antibiotic group). However, the rate of response in this study is significantly higher than placebo studies which have shown “~1 in 6” who experienced fistula closure.

My take: Vedolizumab is another option for treating Crohn’s disease with perianal fistula. Both regimens in this study were associated with response, though the additional 10-week dose (in one group) did not improve outcomes.

Related blog posts:

“Temporary” Diversion for Distal Crohn’s Disease & Latest COVID Stats

AL Lightner et al. Inflamm Bowel Dis 2022; 28: https://doi.org/10.1093/ibd/izab126. Is Intestinal Diversion an Effective Treatment for Distal Crohn’s Disease?

In this retrospective study (n=132 adults), the indications for surgery were medically refractory proctocolitis with perianal disease (n = 59; 45%), perianal disease alone (n = 24; 18%), colitis (n = 37; 28%), proctitis (n = 4; 3%), proctocolitis alone (n = 4; 3%), and ileitis with perianal disease (n = 4; 3%)

Key findings :

  • The clinical and endoscopic response to diversion was 43.2% (n = 57) and 23.9% (n = 16).
  • At a median follow-up of 35.3 months, 25 patients (19%) had improved and had ileostomy reversal, but 86 (65%) did not improve, with 50 (38%) undergoing total proctocolectomy for persistent symptoms
  • Also, 24% experienced stoma morbidity (peristomal abscess, hernia or prolapse)

My take: In this study of adults with distal Crohn’s disease, a “temporary” stoma/fecal diversion was only temporary in ~20%. This information is quite important for patients when considering this treatment option.

Associated commentary: NEK Wieghard. Inflamm Bowel Dis 2022; 28: 325-326. The Difficulty of Distal Crohn’s Disease and the Utility of Diverting Stomas

From March 8, 2022

Silent Anal Fistulas –Sounds Bad, Is It?

A recent prospective study (PH Kim et al. Clin Gastroenterol Hepatol 2020; 18: 415-23) with 440 consecutive adults (mean age 29.6 years) with Crohn’s disease (CD) identified asymptomatic anal fistulas with MRE (including anal MRI) studies. 36 patients were newly diagnosed and the remainder had established CD.

Key findings:

  • In all of these patients, none of whom had clinical fistulas, an MRE identified “perianal tracts” in 53 (12%).
  • 37 of 290 (12.8%) of patients without a perianal fistula history and 16 of 150 (10.7%) with a history of healed perianal fistula had perianal tracts identified on MRE
  • No patients had any lesions that required treatment after examination by a surgeon
  • MRE detection of asymptomatic tracts was independently associated with later need for perianal treatment: 17.8% cumulative incidence at 37 months (aHR 3.06)

My take: Abnormal perianal tracts on MRE in asymptomatic patients indicate an increased risk of developing clinically-significant perianal disease –though most do not.

More on COVID19:

  • No children with IBD have been reported thus far from ESPGHAN which includes a 100 sites (mainly Europe) (as of March 10th); to report cases: ESPGHAN COVID19 Case Report Page
  • There is some discussion that biologic therapy for IBD may have some protective effects

 

 

ADMIRE Study: Use of Stem Cell Therapy for Complex Perianal Fistulas in Crohn’s Disease

A recent phase 3 randomized, double-blind, placebo-controlled study (J Panes et al. Gastroenterol 2018; 154: 1334-42) examined the use of stem cell therapy for the treatment of complex perianal fistulas in Crohn’s disease (CD).

They used a single local injection of 120 million Cx601, a suspension of allogeneic expanded adipose-derived stem cells, and compared to a placebo injection.  This study comprised 212 patients from 49 centers. The primary endpoint, labelled “combined remission,” was based on absence of draining fistulas and MRI findings.

Key Findings:

  • As noted in Figure 1 (below), combined remission occurred in 51.5% of Cx601-Rx patients compared with 35.6% for placebo at week 24; at week 52, combined remission occurred in 56.3% of Cx601-Rx patients compared with 38.6%

My take: This local therapy improved outcomes for 1 year after a single injection and appears promising for refractory perianal fistulas.  It may help avoid surgery or systemic immunosuppression.

 

Closer Look at Data Then Image Below