What is effective in treating refractory Crohn's (Crohn's disease) fistula?

Infliximab is the Most Effective Treatment for Refractory Crohn's Fistula

Infliximab is the most effective treatment option for refractory Crohn's fistula, with strong evidence supporting its use as first-line biological therapy for complex perianal fistulae. 1

Effectiveness of Treatment Options

Infliximab

• Infliximab is FDA-approved for "reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn's disease" 2
• The British Society of Gastroenterology strongly recommends infliximab as first-line biological therapy for complex perianal fistulae, with treatment initiated as soon as adequate drainage of sepsis is achieved 1
• In dedicated randomized controlled trials, infliximab achieved significantly higher rates of fistula closure (48% vs placebo) within 18 weeks 1
• Maintenance therapy with infliximab significantly reduces hospitalizations, surgeries, and procedures in patients with fistulizing Crohn's disease 3
• Higher infliximab trough levels (≥10.1 mcg/mL) are associated with better perianal fistula healing outcomes 4

Other Biological Agents

• Adalimumab and ustekinumab show some effectiveness for fistula healing but with lower quality evidence compared to infliximab 1
• Vedolizumab demonstrated higher rates of closure of draining fistulae at 1 year (41.2% on 8-weekly dosing) compared to placebo 1
• Combination therapy of biologics with antibiotics is more effective than biologics alone 1

Prednisone

• No evidence supports prednisone for treating Crohn's fistulas 1
• Corticosteroids are not mentioned in any guidelines as effective treatment for fistulizing Crohn's disease 1

Azathioprine

• While azathioprine may have some role in fistula management, it is not recommended as monotherapy for refractory fistulas 1
• Azathioprine may be used as an adjunctive treatment in combination with biologics 1, 5
• Combination of infliximab with azathioprine/6-MP may prolong the effect of infliximab on fistula closure 5

Total Parenteral Nutrition (TPN)

• No evidence supports TPN as an effective primary treatment for refractory Crohn's fistulas 1
• TPN is not mentioned in any guidelines as a recommended treatment for fistulizing Crohn's disease 1

Treatment Algorithm for Refractory Crohn's Fistula

1. First-line therapy: Infliximab (5 mg/kg at weeks 0,2, and 6, followed by maintenance every 8 weeks) 1, 2

   • Should be started as soon as adequate drainage of sepsis is achieved 1
   • Consider combination with antibiotics for improved outcomes 1

2. For patients who lose response to infliximab:

   • Consider dose escalation to 10 mg/kg 2
   • Measure infliximab trough levels and aim for ≥10.1 mcg/mL 4
   • Consider adding immunomodulators like azathioprine if not already on combination therapy 5

3. For patients who fail infliximab therapy:

   • Consider alternative biologics: adalimumab, ustekinumab, or vedolizumab 1
   • Surgical options may be considered but have poor long-term results 1

4. For severe, therapy-refractory disease:

   • Faecal stream diversion can be considered, though rates of subsequent successful reversal are low 1
   • Proctectomy may ultimately be required in severe cases 1

Common Pitfalls and Caveats

• Antibiotics alone are not effective for inducing fistula remission in perianal Crohn's disease 1
• Surgical options should only be offered in selected patients after counseling, as long-term results are poor, particularly for those with complex disease and ongoing disease activity 1
• Prednisone and total parenteral nutrition lack evidence for effectiveness in treating Crohn's fistulas 1
• Patients should be assessed for rectal mucosa inflammation (proctitis) as its presence is associated with lower rates of fistula healing 1
• Adequate drainage of sepsis is essential before starting biological therapy 1
• Multiple treatment modalities are often needed to control perianal fistulae in Crohn's disease 1