What is the treatment for fistulizing Crohn's disease?

Treatment of Fistulising Crohn's Disease

Infliximab is strongly recommended as the first-line treatment for induction and maintenance of remission in patients with complex perianal fistulising Crohn's disease. 1

First-Line Treatment Options

Anti-TNF Agents

• Infliximab: The most robust evidence supports infliximab for fistulising Crohn's disease

  • Dosing: 5 mg/kg IV at weeks 0,2, and 6 for induction, followed by maintenance dosing every 8 weeks 1, 2
  • Efficacy: Complete response (absence of draining fistulae) in 46% of patients vs 12.9% with placebo (RR: 3.57; 95% CI: 1.38–9.25) 1
  • Maintenance efficacy: 34.4% maintained complete response at week 54 vs 19.2% with placebo 1

• Adalimumab: May be used when infliximab is not suitable

  • Weaker recommendation (conditional) with lower quality evidence 1
  • Less robust data compared to infliximab, but post-hoc analyses show efficacy (RR: 2.57; 95% CI: 1.13–5.84) for fistula healing 1

Second-Line Treatment Options

• Ustekinumab: Suggested for patients with perianal fistulae who have failed anti-TNF therapy 1

  • Particularly for patients with primary non-response to infliximab

• Vedolizumab: May be considered for patients with perianal fistulae who have failed anti-TNF therapy 1

  • Less evidence than ustekinumab for fistulising disease

Surgical Management Considerations

• Initial abscess drainage: Any perianal abscess should be drained before initiating biological therapy 3
• Seton placement: Often used in combination with medical therapy for complex fistulae 3
• Fistulotomy: Only considered for simple perianal fistulae 3

Combination Therapy

• Antibiotics: Not recommended as monotherapy for fistula remission 1

  • May be used as adjunctive therapy with biologics

• Immunomodulators: Insufficient evidence regarding adding immunomodulators to anti-TNF therapy specifically for fistula healing 1

  • However, combination therapy may reduce immunogenicity and improve overall outcomes 4

Treatment Algorithm

1. Initial assessment:

   • MRI of pelvis and rectum to define fistula anatomy
   • Examination under anesthesia
   • Drainage of any abscesses

2. Induction therapy:

   • Start infliximab 5 mg/kg at weeks 0,2, and 6
   • Consider seton placement for complex fistulae

3. Maintenance therapy:

   • Continue infliximab 5 mg/kg every 8 weeks
   • Monitor for clinical response (reduced or absent fistula drainage)

4. For inadequate response or loss of response:

   • Optimize infliximab dose (up to 10 mg/kg) and/or frequency
   • Consider therapeutic drug monitoring
   • Switch to adalimumab, ustekinumab, or vedolizumab

Important Considerations and Pitfalls

• Treatment goals: Reduction or elimination of fistula drainage, absence of abscesses, and patient satisfaction 3
• Monitoring: MRI imaging is required to demonstrate definitive fistula closure 3
• Long-term therapy: Most patients require long-term maintenance therapy as relapse rates are high upon discontinuation 5
• Screening: Screen for tuberculosis and other infections before initiating anti-TNF therapy 2, 4
• Combination therapy: Consider adding immunosuppressants to reduce antibody formation and improve outcomes 4

Special Situations

• Non-perianal fistulae (enterocutaneous, rectovaginal):

  • Infliximab is also indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas 2
  • Intestinal resection is almost always needed for symptomatic non-perianal fistulas 3

• Treatment failure:

  • For patients with primary non-response to infliximab, ustekinumab is recommended 1
  • For secondary non-response to infliximab, adalimumab or ustekinumab is recommended 1

Infliximab maintenance therapy has been shown to reduce hospitalizations, surgeries, and procedures in patients with fistulising Crohn's disease, making it the cornerstone of treatment for this challenging condition 6.