What is the best management for a patient with Crohn's disease on infliximab (chimeric monoclonal antibody against tumor necrosis factor-alpha) presenting with a perianal discharging fistula, induration, and low-grade fever for 3 weeks?

From the Guidelines

The best management for a patient with Crohn's disease on infliximab presenting with a perianal discharging fistula, induration, and low-grade fever for 3 weeks involves a multidisciplinary approach, starting with surgical drainage of any perianal abscess, followed by antibiotic therapy and optimization of infliximab dose to achieve target levels >10 μg/mL, as higher doses may be beneficial for perianal fistulizing disease 1.

Key Components of Management

• Initial management should include surgical drainage of any perianal abscess to address the infectious component and prevent further complications.
• Antibiotic therapy with ciprofloxacin and metronidazole for 2-4 weeks can help control local sepsis and reduce drainage, as suggested by clinical practice guidelines 1.
• Infliximab therapy should be continued, with consideration of dose optimization to 10 mg/kg every 8 weeks if the current regimen is inadequate, based on evidence that higher doses may improve response in perianal fistulizing disease 1.
• An MRI of the pelvis should be obtained to assess fistula anatomy and exclude undrained collections, guiding further management decisions.
• Consultation with colorectal surgery is essential for potential seton placement to facilitate drainage and prevent recurrent abscess formation, as recommended by ECCO guidelines 1.

Rationale

The presence of fever and induration suggests a possible abscess that requires drainage before effective healing can occur. Maintaining immunosuppression with infliximab is crucial for long-term fistula healing, given its proven efficacy in fistulizing Crohn's disease 1. The combination of surgical drainage, antibiotic therapy, and optimized infliximab dosing addresses both the infectious and inflammatory components of the disease, aiming to achieve complete fistula closure and improve quality of life. Recent guidelines support the use of anti-TNF therapy, such as infliximab, for the induction and maintenance of remission in moderate to severe Crohn's disease, including fistulizing disease 1.

From the FDA Drug Label

Fistulizing Crohn's Disease The safety and efficacy of infliximab were assessed in 2 randomized, double-blind, placebo-controlled studies in patients with fistulizing Crohn's disease with fistula(s) that were of at least 3 months duration. Concurrent use of stable doses of corticosteroids, 5-aminosalicylates, antibiotics, MTX, 6-mercaptopurine (6-MP) and/or azathioprine (AZA) was permitted In the first trial, 94 patients received 3 doses of either placebo or infliximab at Weeks 0,2 and 6. Fistula response (≥ 50% reduction in number of enterocutaneous fistulas draining upon gentle compression on at least 2 consecutive visits without an increase in medication or surgery for Crohn's disease) was seen in 68% (21/31) of patients in the 5 mg/kg infliximab group (P = 0. 002) and 56% (18/32) of patients in the 10 mg/kg infliximab group (P = 0.021) vs. 26% (8/31) of patients in the placebo arm.

The best management for a patient with Crohn's disease on infliximab presenting with a perianal discharging fistula, induration, and low-grade fever for 3 weeks is to use antibiotics before assessing the infliximab level, as the concurrent use of antibiotics is permitted in the treatment of fistulizing Crohn's disease.

• Key points:
  • The patient is already on infliximab, which has shown efficacy in treating fistulizing Crohn's disease.
  • The use of antibiotics is allowed in conjunction with infliximab.
  • There is no direct information in the label to suggest increasing the dose of infliximab or using an MRI as the first step in management.
  • The patient's symptoms, such as induration and low-grade fever, may indicate an infection that requires antibiotic treatment.
  • Assessing the infliximab level after antibiotic treatment can help determine the next steps in management, such as adjusting the dose or continuing with the current treatment plan 2.

From the Research

Management of Perianal Discharging Fistula in Crohn's Disease

• The patient presents with a perianal discharging fistula, induration, and low-grade fever for 3 weeks while on infliximab, a chimeric monoclonal antibody against tumor necrosis factor-alpha 3.
• The first step in management would be to assess for any infections, as the presence of a fistula and low-grade fever suggests a possible infectious complication.
• According to a study on the impact of time to antibiotic therapy on clinical outcome in patients with bacterial infections, withholding antibiotic therapy until diagnostic results are available and a diagnosis has been established seems acceptable in most cases unless septic shock or bacterial meningitis are suspected 4.
• However, in the case of a perianal discharging fistula, antibiotics may be necessary to manage any underlying infection, and the choice of antibiotic should be guided by culture and sensitivity results from a swab of the discharge 5.
• A study on individualized antibiotic therapy in the treatment of severe infections highlights the importance of early pathogen identification and optimal drug regimens based on pharmacokinetic/pharmacodynamics (PK/PD) 6.
• In terms of managing the Crohn's disease itself, a systemic review and meta-analysis found that combination therapy of biologics and immunosuppressants is preferential to inducing clinical remission in patients with active inflammatory bowel disease 7.
• Therefore, the best management for this patient would be to:
  • Take a swab from the discharge for culture and sensitivity testing to guide antibiotic therapy.
  • Consider adding or adjusting antibiotics based on the results of the culture and sensitivity testing.
  • Assess the patient's infliximab level to determine if the current dose is adequate or if an adjustment is needed.
  • Consider adding an immunosuppressant to the patient's treatment regimen if not already on one, as combination therapy may be more effective in inducing clinical remission.
• Among the given options, B. Antibiotics then assess infliximab level seems to be the most appropriate initial step, as it addresses the potential infection and evaluates the current treatment regimen for Crohn's disease.