What is the recommended dose of infliximab (chimeric monoclonal antibody against tumor necrosis factor-alpha) for managing fistula in ano in a patient with ulcerative colitis (UC)?

Management of Fistula in Ano with Infliximab in Ulcerative Colitis Patients

For managing fistula in ano in patients with 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 for Fistulizing Disease

Induction Phase

• Initial dose: 5 mg/kg intravenously
• Dosing schedule: Weeks 0,2, and 6
• This three-dose induction regimen is the preferred strategy for inducing remission 1

Maintenance Phase

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

Evidence Supporting This Approach

While fistulizing disease is more commonly associated with Crohn's disease, the management principles apply to UC patients with fistula in ano. The American Gastroenterological Association guidelines specifically state that infliximab at a dose of 5 mg/kg administered as a 3-dose induction regimen is effective for reducing the number of draining fistulas and for closure of all fistulas 1.

In clinical trials for fistulizing disease:

• 68% of patients receiving 5 mg/kg infliximab achieved at least 50% reduction in draining fistulas compared to 26% with placebo 2
• Complete fistula closure was observed in 55% of patients receiving 5 mg/kg infliximab 2
• Maintenance therapy with infliximab 5 mg/kg every 8 weeks prolongs the time to loss of response 3

Combination Therapy Considerations

Adding an immunomodulator to infliximab therapy is recommended:

• Combination with a thiopurine (azathioprine or 6-mercaptopurine) is more efficacious than infliximab alone 1
• Combination therapy reduces immunogenicity and antibody formation against infliximab 4
• Statement 20 from the Alimentary Pharmacology & Therapeutics guidelines explicitly states: "If infliximab is used for maintenance therapy, the combination of a thiopurine with infliximab is more efficacious than infliximab alone" 1

Dose Optimization and Monitoring

If inadequate response occurs with standard dosing:

• Consider measuring serum infliximab trough concentrations
• Target trough levels >10μg/mL are associated with better clinical outcomes 4
• Options for dose optimization include:
  1. Shortening the dosing interval (e.g., every 6 weeks instead of 8)
  2. Increasing the dose up to 10 mg/kg if needed 4

Important Considerations and Precautions

• Pre-treatment screening: All patients should be screened for tuberculosis prior to initiating infliximab therapy 1
• Contraindications: Active infection is an absolute contraindication 1
• Monitoring: Regular assessment of clinical response, inflammatory markers, and drug levels is essential 4
• Surgical management: Combined medical-surgical approach may be necessary for complex fistulae, with seton placement often required prior to infliximab therapy 1

Common Pitfalls to Avoid

1. Inadequate induction: Skipping the full three-dose induction regimen may result in suboptimal response
2. Monotherapy in high-risk patients: Failing to add an immunomodulator increases the risk of antibody formation and loss of response
3. Delayed dose optimization: Waiting too long to adjust dosing when response is inadequate
4. Treating without addressing sepsis: Any abscess must be drained before starting infliximab to avoid overwhelming septicemia 1
5. Discontinuing too early: Premature discontinuation often leads to recurrence of fistulae

By following this evidence-based approach with appropriate dosing, combination therapy when indicated, and careful monitoring, optimal outcomes for fistula in ano can be achieved in patients with ulcerative colitis.