What is the stepwise management of fistulizing Crohn's disease (Crohn's disease)?

From the Guidelines

The management of fistulising Crohn's disease requires a stepwise approach combining medical and surgical interventions, with anti-TNF agents as the mainstay of medical therapy, and infliximab being the first-line biologic at an induction dose of 5mg/kg at weeks 0,2, and 6, followed by maintenance every 8 weeks, as recommended by the AGA clinical practice guidelines 1. The initial treatment should focus on controlling sepsis through drainage of any abscesses and administration of antibiotics such as ciprofloxacin 500mg twice daily and/or metronidazole 500mg three times daily for 2-4 weeks. Once sepsis is controlled, the use of infliximab is recommended over no treatment for induction and maintenance of remission, with a strong recommendation and moderate certainty of evidence 1. Adalimumab (160mg at week 0, 80mg at week 2, then 40mg every 2 weeks) is an alternative if infliximab is contraindicated. For complex perianal fistulas, a combination of antibiotics, anti-TNF therapy, and surgical placement of non-cutting setons is often necessary, with examination under anesthesia recommended to assess the rectal mucosa and guide further management 1. Some key points to consider in the management of fistulising Crohn's disease include:

• The use of biologic drug monotherapy over thiopurine monotherapy for the induction of remission, with a strong recommendation and moderate certainty of evidence 1
• The consideration of ustekinumab or vedolizumab as second-line biologics for refractory cases, with a strong recommendation and moderate certainty of evidence for ustekinumab 1
• The importance of nutritional support and regular monitoring with MRI and examination under anesthesia to assess fistula healing
• The potential benefits and risks of surgical interventions, including fistulotomy, advancement flaps, and diverting ostomy, with variable reported efficacy and potential for progressive failure over time 1

From the FDA Drug Label

RENFLEXIS is indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn's disease. The recommended dose of RENFLEXIS is 5 mg/kg given as an intravenous induction regimen at 0,2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of adults with moderately to severely active Crohn's disease or fistulizing Crohn's disease

The stepwise management of fistulising Crohn’s disease with infliximab (IV) involves:

• Induction regimen: 5 mg/kg at 0,2, and 6 weeks
• Maintenance regimen: 5 mg/kg every 8 weeks For patients who respond and then lose their response, consideration may be given to treatment with 10 mg/kg. Patients who do not respond by Week 14 are unlikely to respond with continued dosing and consideration should be given to discontinue RENFLEXIS in these patients 2.

From the Research

Stepwise Management of Fistulising Crohn's Disease

The management of fistulising Crohn's disease involves a stepwise approach, incorporating medical and surgical therapies. The following steps are based on the available evidence:

• Initial investigation:
  • Imaging (MRI of the pelvis and rectum) 3
  • Examination under anaesthesia (EUA) with digital imaging, endoscopy, probing, and anal ultrasound 3
  • Contrast imaging and/or CT/MRI for non-perianal fistulas 3
• Treatment of abscesses:
  • Drainage of any abscesses 3
• Evaluation of disease extent:
  • Assessment of the disease extent throughout the entire gastrointestinal tract 3
• Medical therapy:
  • Antibiotics and azathioprine or 6-mercaptopurine for complex perianal fistulas 3
  • Infliximab at 5 mg/kg for persistent secretion, given at weeks 0,2, and 6, and subsequently every 8 weeks 3, 4
  • Adalimumab for fistula response in both infliximab-naïve patients and following infliximab treatment failure 3, 5, 6
• Surgical therapy:
  • Fistulotomy for simple perianal fistulas 3
  • Definitive surgical closure of perianal fistulas using an advancement flap, although associated with a high risk of relapse 3
  • Colostomy and proctectomy as ultimate surgical treatment options for fistulas 3
  • Intestinal resection for symptomatic non-perianal fistulas 3

Emerging Therapies

Emerging data suggest the potential benefits of new biologic agents, therapeutic drug monitoring, novel surgical methods, and mesenchymal stem cell therapy in achieving fistula healing 7.

Comparison of Therapies

Network meta-analysis has compared the effectiveness of various therapies, including infliximab, adalimumab, and azathioprine, for inducing and maintaining remission in Crohn's disease 6. The results suggest that adalimumab and infliximab + azathioprine are the most effective therapies for induction and maintenance of remission 6.