What is the best next step in management for a patient with Crohn's disease and perianal fistulae, currently on steroids and Pentasa (mesalamine), with well-controlled abdominal symptoms but persistent perineal pain and discharges?

Management of Perianal Fistulae in Crohn's Disease

Infliximab is the best next step in management for this patient with Crohn's disease and perianal fistulae. 1

Rationale for Infliximab Selection

The 30-year-old male patient presents with:

• Ileocolonic Crohn's disease currently on steroids and Pentasa (mesalamine)
• Well-controlled abdominal symptoms
• New development of perianal fistulae (confirmed by MRI)
• Laboratory evidence of ongoing inflammation (elevated ESR, low hemoglobin)

According to the American Gastroenterological Association (AGA) clinical practice guidelines, infliximab has the strongest evidence for treating perianal fistulizing Crohn's disease:

1. Infliximab is the only medication with a dedicated randomized controlled trial specifically assessing efficacy for fistula remission 1
2. The AGA provides a strong recommendation (moderate certainty evidence) for infliximab over no treatment for both induction and maintenance of fistula remission 1
3. Infliximab achieved a significantly greater rate of fistula closure within 18 weeks compared to placebo (RR, 0.52; 95% CI, 0.34-0.78) 1

Why Not the Other Options?

Azathioprine (Option B)

• While thiopurines like azathioprine are sometimes used in Crohn's disease, the AGA guidelines note that data on thiopurines for perianal fistulizing disease is quite limited 1
• Biologic agents have demonstrated superior efficacy compared to thiopurine monotherapy 1
• Recent evidence suggests that infliximab in combination with azathioprine may be more effective than either agent alone, but infliximab remains the primary agent 2

Methotrexate (Option C)

• There is insufficient evidence supporting methotrexate as monotherapy for perianal fistulizing Crohn's disease 1
• The AGA guidelines do not recommend methotrexate for this indication 1

Budesonide (Option D)

• Corticosteroids, including budesonide, are not recommended for maintenance therapy in Crohn's disease 1
• There is no evidence supporting budesonide for perianal fistulizing disease 1
• The patient is already on steroids, which have not prevented the development of perianal fistulae

Optimizing Treatment Approach

1. Initial management:

   • Rule out perianal abscess before starting biologics 3
   • If abscess is present, drainage is essential before adjusting immunosuppressive therapy 3

2. Combination therapy:

   • Consider adding antibiotics to infliximab for induction therapy
   • The AGA strongly recommends biologic agents in combination with antibiotics over biologic drug alone for induction of fistula remission 1
   • Typically ciprofloxacin 500mg twice daily for 12 weeks with infliximab 1

3. Dosing considerations:

   • Standard infliximab dosing is 5 mg/kg at weeks 0,2, and 6, followed by maintenance every 8 weeks 4
   • Higher trough levels (≥10.1 μg/mL) are associated with better fistula healing rates 5, 6

4. Monitoring response:

   • Assess for clinical response (reduction in drainage)
   • Consider follow-up MRI to evaluate fistula tract healing
   • Therapeutic drug monitoring to ensure adequate infliximab levels 6

Important Considerations

• Current medications: The patient is on Pentasa (mesalamine), which the AGA specifically recommends against for moderate to severe Crohn's disease due to lack of efficacy 1
• Combination therapy: Consider continuing azathioprine with infliximab for potentially improved outcomes, though this must be balanced against increased risk of immunosuppression 3
• Surgical evaluation: Consider surgical consultation for possible seton placement if fistulae don't respond to medical therapy 3

Treatment Algorithm

1. Start infliximab 5 mg/kg at weeks 0,2, and 6, then every 8 weeks
2. Add ciprofloxacin 500mg twice daily for 12 weeks
3. Consider discontinuing Pentasa as it lacks efficacy for moderate-severe Crohn's disease
4. Gradually taper steroids once clinical response is achieved
5. Monitor infliximab trough levels and aim for ≥10 μg/mL for perianal fistulizing disease
6. Reassess fistula response at weeks 10-14; if inadequate response, consider dose escalation

Recent evidence from 2023 confirms that infliximab has superior efficacy compared to adalimumab for first-line treatment of Crohn's perianal fistulae, with significantly higher rates of response and remission at both 6 and 12 months 2.