What is the most appropriate medication regimen for maintaining remission in a 24-year-old male with Crohn’s disease (CD), who has high thiopurine methyltransferase (TPMT) activity, and recently achieved remission with infliximab (chimeric monoclonal antibody against tumor necrosis factor-alpha (TNF-alpha)) and prednisone?

Optimal Maintenance Therapy for Moderate-to-Severe Crohn's Disease in Remission

Azathioprine 75 mg orally twice daily plus infliximab 375 mg intravenously every 8 weeks is the most appropriate medication regimen for maintaining remission in this 24-year-old male with Crohn's disease.

Rationale for Combination Therapy

The combination of infliximab and azathioprine has demonstrated superior efficacy in maintaining remission in Crohn's disease compared to monotherapy options. This approach is strongly supported by multiple clinical guidelines:

• The Canadian Association of Gastroenterology strongly recommends anti-TNF therapy (infliximab) for maintaining complete remission in Crohn's disease 1
• When starting anti-TNF therapy, guidelines suggest combining it with a thiopurine to improve efficacy and pharmacokinetic parameters 1
• The ECCO guidelines specifically recommend combination therapy with infliximab and thiopurines for a minimum of 6-12 months when using infliximab as maintenance therapy 1

Dosing Considerations

The appropriate dosing for this patient is:

• Infliximab: 5 mg/kg IV every 8 weeks (which equals 375 mg for this 75 kg patient)
• Azathioprine: 2-2.5 mg/kg/day (75 mg twice daily is appropriate for this 75 kg patient with high TPMT activity)

The FDA label for infliximab confirms the recommended maintenance dose of 5 mg/kg every 8 weeks for Crohn's disease 2.

Why This Regimen Is Superior to the Alternatives

1. Extended-release mesalamine + ustekinumab:

   • 5-ASA agents (mesalamine) have not shown efficacy in Crohn's disease maintenance therapy 1
   • While ustekinumab is effective, it's typically reserved for patients who have failed anti-TNF therapy 3

2. Prednisone + azathioprine:

   • Long-term corticosteroid use is not recommended for maintenance therapy due to side effects
   • The goal is to achieve corticosteroid-free remission 1

3. Sulfasalazine monotherapy:

   • Sulfasalazine has not demonstrated efficacy for maintenance of remission in Crohn's disease 1

Evidence Supporting Combination Therapy

The SONIC trial demonstrated that combination therapy with infliximab and azathioprine was superior to either agent alone for maintaining remission 4. Patients receiving combination therapy had:

• Higher rates of corticosteroid-free remission
• Better mucosal healing
• Lower immunogenicity (fewer anti-drug antibodies)
• Higher serum infliximab concentrations

The ACCENT I trial established that patients who respond to infliximab induction are more likely to maintain remission at weeks 30 and 54 when continuing infliximab maintenance therapy every 8 weeks 5.

Patient-Specific Considerations

For this specific patient:

• He has already responded to infliximab induction therapy
• His high TPMT activity indicates he can safely receive standard azathioprine dosing
• He is negative for JC virus antibodies, reducing the risk of progressive multifocal leukoencephalopathy
• At 24 years old, he is at higher risk for disease progression without effective maintenance therapy

Safety Considerations

While combination therapy is most effective, there are important safety considerations:

• Young males on combination therapy have an increased risk of hepatosplenic T-cell lymphoma (HSTCL) 2
• Regular monitoring for adverse effects is essential, including complete blood counts and liver function tests
• After 6-12 months of successful combination therapy, consideration can be given to withdrawing the thiopurine while continuing infliximab monotherapy 1, 6

Monitoring Recommendations

• Evaluate clinical response between 8-12 weeks after initiating maintenance therapy 1
• Assess for mucosal healing with endoscopy within the first year 1
• Monitor for immunogenicity with therapeutic drug monitoring if response is suboptimal 1
• Regular laboratory monitoring for myelosuppression and hepatotoxicity

In conclusion, the combination of azathioprine 75 mg twice daily plus infliximab 375 mg IV every 8 weeks represents the optimal evidence-based approach for maintaining remission in this patient with moderate-to-severe Crohn's disease.