What is the recommended dose of Infliximab (infliximab) for treating complicated perianal fistula in Ulcerative Colitis (UC)?

Infliximab Dosing for Complicated Perianal Fistula in Ulcerative Colitis

For complicated perianal fistulas in ulcerative colitis, infliximab should be administered at a dose of 5 mg/kg at weeks 0,2, and 6 for induction, followed by maintenance dosing every 8 weeks. 1

Dosing Regimen Details

Induction Phase

• Initial dose: 5 mg/kg intravenously 1, 2
• Timing: Weeks 0,2, and 6 1, 3
• This three-dose induction regimen is the preferred strategy for initiating treatment 1

Maintenance Phase

• Dose: Continue with 5 mg/kg 2
• Frequency: Every 8 weeks 1, 3
• Duration: Long-term maintenance therapy is typically required to sustain fistula closure 1

Dose Optimization

If inadequate response occurs with standard dosing, consider:

1. Measuring serum infliximab trough concentrations

   • Target trough levels >10 μg/mL are associated with better clinical outcomes for fistula healing 1

2. Dose adjustment options:

   • Shortening the dosing interval (more frequent than every 8 weeks) 1
   • Increasing the dose up to 10 mg/kg if needed 1, 2

Combination Therapy Approach

Adding an immunomodulator to infliximab is strongly recommended:

• Combination with a thiopurine (azathioprine 1.5-2.5 mg/kg/day or 6-mercaptopurine 0.75-1.5 mg/kg/day) is more efficacious than infliximab alone 1, 3
• This combination reduces immunogenicity and antibody formation against infliximab 1

Surgical Considerations

A combined medical-surgical approach is often necessary:

• Any abscess must be drained before starting infliximab to avoid septicemia 1
• Examination under anesthesia with seton placement prior to infliximab therapy improves outcomes 4
• This combined approach results in:
  • Better initial response rates
  • Lower recurrence rates
  • Longer time to recurrence 4

Pre-treatment Requirements

Before initiating infliximab:

• Screen for tuberculosis 1, 5
• Ensure there is no active infection (absolute contraindication) 1, 5
• Evaluate for any contraindications to immunosuppressive therapy

Monitoring

Regular assessment should include:

• Clinical response evaluation
• Inflammatory markers
• Drug levels, particularly if response is suboptimal 1

Important Considerations

1. While most evidence for perianal fistula treatment comes from Crohn's disease studies 3, the same dosing principles apply to ulcerative colitis patients with this complication.

2. The ACCENT II trial demonstrated that patients receiving infliximab maintenance therapy (5 mg/kg every 8 weeks) had significantly longer time to loss of response compared to placebo (>40 weeks vs. 14 weeks) 6.

3. Complete fistula closure rates at week 54 were significantly higher with infliximab maintenance (36%) compared to placebo (19%) 6.