What is the recommended treatment approach for fistulizing Crohn's disease?

Treatment of Fistulizing Crohn's Disease

Infliximab 5 mg/kg at weeks 0,2, and 6, then every 8 weeks, combined with surgical drainage of any abscess and loose seton placement, is the first-line treatment for complex perianal fistulizing Crohn's disease. 1

Initial Assessment and Sepsis Control

Examination under anesthesia (EUA) by an experienced colorectal surgeon must be performed immediately to drain any abscess and place a loose non-cutting seton before starting anti-TNF therapy. 1 Active sepsis is an absolute contraindication to infliximab per FDA labeling. 2

• Obtain pelvic MRI before or shortly after EUA to map fistula anatomy and identify occult abscesses 1, 3
• Perform proctosigmoidoscopy to assess for active proctitis, which dramatically reduces surgical success rates and must be treated medically first 1
• More than two-thirds of patients have an associated abscess requiring drainage before definitive therapy 3

Medical Therapy Algorithm

Start infliximab 5 mg/kg at weeks 0,2, and 6, then every 8 weeks as soon as adequate surgical drainage is achieved. 1 This is the strongest recommendation from the most recent (2025) British Society of Gastroenterology guidelines. 1

Infliximab Dosing and Monitoring

• Standard dosing achieves complete fistula closure in up to 55% of patients during induction 1
• For patients who initially respond but later lose response, escalate to 10 mg/kg every 8 weeks 1
• Target serum trough levels >10 μg/mL for optimal fistula healing outcomes 1
• Maintenance therapy significantly improves sustained response (RR 1.88) and remission (RR 1.79) compared to placebo 1

Combination Immunosuppression

Add azathioprine (2.0-2.5 mg/kg) or 6-mercaptopurine (1.0-1.5 mg/kg) to infliximab therapy. 1, 4, 5 While ACCENT II subgroup analysis showed no benefit, more recent studies demonstrate clear association between combination therapy and fistula closure, particularly in patients with proctitis. 1

Antibiotic Therapy

Ciprofloxacin 1000 mg daily and/or metronidazole 1500 mg daily should be added during the acute phase to manage sepsis and in conjunction with advanced medical therapy. 1, 4, 5 Antibiotics alone show no benefit for fistula closure but are valuable adjuncts. 1

Surgical Management Strategy

Seton Management

The loose non-cutting seton should remain in place long-term to prevent recurrent abscess formation. 1, 3 Seton drainage combined with anti-TNF therapy shows superior outcomes (71.3% response) compared to surgery alone (35.9%). 1

• Remove the seton only after clinical assessment shows cessation of drainage, typically after completing the infliximab induction phase (approximately 1 month) 6, 7
• Never use cutting setons—they cause 57% incontinence rates from progressive sphincter transection 3, 6

Definitive Surgical Repair

Definitive surgical procedures (advancement flaps, LIFT, fistula plugs) should only be attempted after achieving endoscopic remission of proctitis and optimizing medical therapy. 1 The 2019 British Society guidelines explicitly state these procedures have poor long-term results, particularly in complex disease. 1

• Mucosal advancement flaps: 64% success rate but 50% require re-intervention 1, 3
• LIFT procedure: 56-94% healing in primary cases, but only 53% in Crohn's disease 1, 3
• Fibrin glue: 38% remission at 8 weeks (vs 16% placebo), but long-term efficacy unclear 1
• Fistula plugs: 55% success but 22% dislodgement rate 1, 3

Active proctitis is an absolute contraindication to any definitive closure procedure. 1, 3

Advanced and Salvage Therapies

Adipose-Derived Stem Cells

Allogeneic adipose-derived stem cells (darvadstrocel) 120 million cells as a single intralesional injection achieved 50% complete remission at 24 weeks versus 34% placebo in the phase III ADMIRE-CD trial. 1 This is reserved for treatment-refractory complex perianal fistulas after failure of at least one of antibiotics, immunomodulators, or anti-TNF therapy. 1

Faecal Diversion

Faecal stream diversion with a temporary stoma can be used for severe refractory perianal Crohn's disease, but patients must be counseled that reversal rates are low (26-50% sustained remission) and most ultimately require proctectomy. 1 Early use of medical therapies post-diversion and absence of proctitis improve chances of restoring bowel continuity. 1

Proctectomy

Proctectomy with permanent stoma is the definitive salvage option for therapy-refractory disease. 1, 3 Risk of proctectomy after defunctioning stoma approaches 68% on long-term follow-up. 1

Monitoring Response

Clinical assessment of decreased drainage is the primary method to evaluate healing. 1, 3 However, there is significant disconnect between cessation of drainage and actual deep healing. 8, 5

• MRI or endoscopic ultrasound (EUS) can identify persistent fistula activity in 48% of patients with clinical cessation of drainage 4, 8, 5
• EUS-guided therapy allows identification of patients who can safely discontinue infliximab without recurrence 4, 5
• In one randomized trial, EUS-guided combination therapy achieved 80% complete cessation of drainage versus 20% in controls 5

Critical Pitfalls to Avoid

Never start infliximab without first draining abscesses and controlling active sepsis—this is an FDA-labeled contraindication. 1, 2

Never perform fistulotomy on complex or high fistulas in Crohn's disease—this causes unacceptable incontinence risk. 3, 6

Never excise perianal skin tags in Crohn's patients—this leads to chronic non-healing ulcers. 3

Never attempt definitive surgical closure in the presence of active proctitis—failure rates approach 100%. 1, 3

Never assume clinical cessation of drainage equals fistula healing—imaging often reveals persistent tract activity. 4, 8, 5