Management of Perianal Fistulae in Crohn's Disease
Infliximab is the best next step in management for this patient with perianal fistulae in Crohn's disease who is currently on steroids and Pentasa. 1
Rationale for Infliximab Selection
Infliximab is the optimal choice for several important reasons:
Strong evidence for fistula healing: Infliximab is the only medication that has a dedicated randomized controlled trial specifically assessing its efficacy for inducing fistula remission in Crohn's disease. It achieved significantly greater rates of fistula closure compared to placebo (68% vs 26%) 1.
Strong recommendation from guidelines: The American Gastroenterological Association (AGA) provides a strong recommendation (with moderate certainty evidence) for the use of infliximab over no treatment for both induction and maintenance of fistula remission in perianal Crohn's disease 1.
Proven efficacy: In clinical trials, infliximab demonstrated complete fistula closure in 36% of patients at week 54 compared to 19% in the placebo group 2.
Superior to other TNF inhibitors: Recent evidence shows that infliximab has superior efficacy compared to adalimumab for first-line treatment of Crohn's perianal fistulae, with significantly higher rates of clinical response at both 6 months (64.9% vs 34.8%) and 12 months 3.
Why Not the Other Options?
Azathioprine (Option B): While thiopurines can be used in Crohn's disease, the AGA guidelines note that data on thiopurines for perianal fistulae are quite limited, and the guideline panel did not find sufficient evidence to formulate a recommendation for their use as monotherapy 1. Thiopurines are more effective when used in combination with infliximab rather than as monotherapy.
Methotrexate (Option C): Similar to thiopurines, there is insufficient evidence supporting methotrexate as monotherapy for perianal fistulae in Crohn's disease 1.
Budesonide (Option D): Corticosteroids, including budesonide, are not recommended for maintenance therapy in Crohn's disease and have no specific role in fistula healing 1.
Optimal Treatment Approach
Start infliximab: The recommended dosing is 5 mg/kg given as an intravenous induction regimen at weeks 0,2, and 6, followed by maintenance therapy every 8 weeks 4.
Consider combination therapy:
- Adding an antibiotic (ciprofloxacin or metronidazole) to infliximab significantly improves outcomes. The AGA strongly recommends using biologic agents in combination with antibiotics over biologic therapy alone for induction of fistula remission 1.
- Consider continuing azathioprine with infliximab for improved efficacy, though this must be balanced against the risk of increased immunosuppression 5.
Target higher trough levels: Aim for infliximab trough levels ≥10 μg/mL, as higher trough levels are associated with better fistula healing rates 6, 7.
Monitoring and Follow-up
- Evaluate response at weeks 10-14 after starting infliximab 1, 4
- Monitor for:
- Clinical response (reduction in drainage)
- Complete fistula closure
- Adverse effects of therapy
- Development of anti-infliximab antibodies, which significantly reduce the chance of fistula healing (OR: 0.04) 6
Important Considerations
Drainage of any abscesses: Before optimizing immunosuppressive therapy, ensure any perianal abscesses are adequately drained to prevent septic complications 5.
Persistence of fistula tracts: Even with clinical closure, endosonographic studies show that most fistula tracts remain detectable, which may explain why relapses are common 8. This underscores the importance of maintenance therapy.
Combination therapy benefits: The combination of infliximab with an immunomodulator like azathioprine may improve outcomes, but must be balanced against the increased risk of opportunistic infections and rare complications like hepatosplenic T-cell lymphoma 1, 4.
Discontinuation of Pentasa: The AGA recommends against the use of 5-ASA medications (like Pentasa) for moderate to severe Crohn's disease, as they lack efficacy for maintenance of remission 1.
By implementing this evidence-based approach with infliximab as the cornerstone of therapy, this patient has the best chance of achieving fistula healing and maintaining remission of their Crohn's disease.