What are the treatment options for Crohn's disease, including medications such as aminosalicylates (e.g. mesalamine), immunomodulators (e.g. azathioprine), biologics (e.g. infliximab), and JAK inhibitors (e.g. tofacitinib)?

Medications for Crohn's Disease

For patients with Crohn's disease, a step-up treatment approach should be replaced with early introduction of biologics with or without immunomodulators for moderate to severe disease, as this strategy improves outcomes related to morbidity, mortality, and quality of life. 1

Treatment Algorithm Based on Disease Severity

Mild Disease

• First-line:
  • Budesonide 9 mg daily for isolated ileo-cecal disease 1
  • Sulfasalazine 4g daily for disease limited to the colon 1, 2

Moderate to Severe Disease

• First-line:
  • Early introduction of biologics (anti-TNF) with or without immunomodulators 1
  • Combination therapy with infliximab and azathioprine is superior to either agent alone 1, 3

Fistulizing/Perianal Disease

• First-line:
  • Metronidazole 400 mg three times daily and/or ciprofloxacin 500 mg twice daily 1
  • For complex fistulae: Anti-TNF therapy (infliximab 5 mg/kg at weeks 0,2, and 6) 1

Medication Classes in Detail

Aminosalicylates (5-ASA)

• Efficacy: Not recommended for Crohn's disease treatment 1
• High-dose mesalamine (4 g/day) may have limited benefit in mild ileocolonic disease, but evidence is weak 1
• Sulfasalazine shows modest efficacy only when disease is confined to the colon 2, 4

Corticosteroids

• Conventional steroids (prednisolone 40 mg daily):

  • Effective for moderate to severe disease 1
  • Should be tapered over 8 weeks 1
  • Not suitable for maintenance therapy due to side effects

• Budesonide (9 mg daily):

  • Preferred for isolated ileo-cecal disease 1
  • Fewer systemic side effects than conventional steroids
  • Nearly as effective as prednisolone 1

Immunomodulators

• Azathioprine (1.5-2.5 mg/kg/day) or 6-mercaptopurine (0.75-1.5 mg/kg/day):

  • Effective as steroid-sparing agents 1
  • Slow onset of action (8-14 weeks) limits use as monotherapy 1
  • Early introduction alone does not significantly improve outcomes compared to conventional management 5

• Methotrexate (15 mg/m² weekly, max 25 mg):

  • Alternative for maintenance therapy when thiopurines fail 1
  • Subcutaneous administration preferred over oral 1
  • Requires folic acid supplementation to minimize side effects 1

Biologics

• Anti-TNF agents (infliximab, adalimumab):

  • Infliximab: 5 mg/kg IV at weeks 0,2,6, then every 8 weeks 1
  • Adalimumab: 160 mg initially, 80 mg at week 2, then 40 mg every other week 6
  • More effective than immunomodulators alone 3
  • Particularly effective for fistulizing disease 1

• Anti-IL-12/23 (ustekinumab):

  • Effective for moderate to severe Crohn's disease 7
  • Option for patients who fail anti-TNF therapy

JAK Inhibitors

• Emerging option for moderate to severe disease
• Consider when biologics have failed

Combination Therapy

• Infliximab + azathioprine is superior to either agent alone for:
  • Achieving clinical remission (56.8% vs 44.4% for infliximab alone and 30% for azathioprine alone) 3
  • Mucosal healing (43.9% vs 30.1% for infliximab alone and 16.5% for azathioprine alone) 3

Common Pitfalls to Avoid

1. Delaying effective therapy: Step-up approach may result in disease progression and complications 1
2. Overreliance on 5-ASA: Aminosalicylates have limited to no efficacy in Crohn's disease 1, 4
3. Prolonged steroid use: Associated with significant side effects; maintenance therapy should utilize steroid-sparing agents
4. Monotherapy with immunomodulators: Less effective than combination therapy with biologics 3
5. Treating without considering disease location: Treatment should be tailored based on disease location (ileal, colonic, etc.) 1

Special Considerations

• Combination therapy increases efficacy but may increase risk of infections and malignancy 1
• Regular monitoring for adverse effects is essential, especially with immunomodulators and biologics
• Surgery should be considered for patients with limited disease who fail medical therapy 1