Duration of Infliximab for Enterocutaneous Fistula in Crohn's Disease
For enterocutaneous fistulas in Crohn's disease, infliximab should be continued as long-term maintenance therapy every 8 weeks indefinitely after induction, as discontinuation leads to loss of response in the majority of patients. 1
Induction Regimen
- Administer infliximab 5 mg/kg at weeks 0,2, and 6 for initial induction therapy in patients with enterocutaneous fistulas refractory to conventional treatment 1
- This three-dose induction regimen is superior to single-dose therapy and should be used as part of a comprehensive strategy that includes immunomodulation and surgical evaluation 1
Maintenance Duration: Indefinite Therapy
The evidence strongly supports continuous, indefinite maintenance therapy rather than episodic treatment:
- Continue infliximab 5 mg/kg every 8 weeks without planned discontinuation 1, 2
- In the pivotal ACCENT II trial, patients receiving scheduled maintenance infliximab every 8 weeks had significantly longer time to loss of response compared to placebo (>40 weeks vs. 14 weeks, P<0.001) 2, 3
- At week 54,36% of patients on infliximab maintenance had complete fistula closure versus 19% on placebo (P=0.009) 2, 3
Why Indefinite Rather Than Time-Limited?
The data demonstrate that stopping therapy leads to relapse:
- The median duration of fistula closure after infliximab is only approximately 12 weeks without maintenance therapy 2, 4
- Patients who achieved response and were randomized to placebo maintenance lost their response at a median of 14 weeks 2, 3
- There is currently no evidence supporting planned withdrawal of biologic agents in patients with fistulizing disease, even with stable long-term remission 1
Combination Therapy Considerations
- Consider adding azathioprine (1.5-2.5 mg/kg/day) or 6-mercaptopurine (0.75-1.5 mg/kg/day) to infliximab for at least the first 6-12 months 1
- Concomitant immunosuppression reduces antibody formation to infliximab, decreases infusion reactions, and may improve long-term outcomes 4, 5
- For luminal Crohn's disease, immunomodulators can be withdrawn after long-term remission, but insufficient evidence exists to recommend this approach specifically for fistulizing disease 1
Dose Escalation Strategy
If loss of response occurs on standard maintenance:
- Increase infliximab dose to 10 mg/kg every 8 weeks 2, 3
- In ACCENT II, 57% of patients who lost response on 5 mg/kg maintenance regained response when escalated to 10 mg/kg 2
- Alternatively, consider shortening the dosing interval (e.g., every 6 weeks) based on therapeutic drug monitoring if available 1
Critical Caveats
- Ensure absence of undrained abscess and distal obstruction before initiating infliximab - these are contraindications that require surgical intervention first 1
- Screen for tuberculosis with PPD testing before starting therapy due to reactivation risk 1, 4
- Patients who do not respond by week 14 are unlikely to benefit from additional infliximab doses and should be considered for alternative strategies 2
- Surgical evaluation with examination under anesthesia and seton placement prior to infliximab may improve outcomes - one study showed 100% initial response vs. 82.6% with infliximab alone, and longer time to recurrence (13.5 vs. 3.6 months) 6
Monitoring During Maintenance
- Assess fistula drainage at each infusion visit (every 8 weeks) 2, 3
- Monitor for infusion reactions, infections, and development of antibodies to infliximab 1, 4, 5
- Consider therapeutic drug monitoring to guide dose optimization if loss of response occurs 1
The decision to eventually discontinue therapy must be individualized, weighing the risk of fistula recurrence (which is high) against long-term medication risks, but current evidence does not support planned discontinuation at any specific timepoint. 1