What are the recommended treatment options for Crohn’s disease based on disease location, severity, and prior therapy?

Treatment Options for Crohn's Disease

For patients with moderate to severe Crohn's disease and high-risk features (stricturing/penetrating disease, perianal fistulas, age <40 years, or steroid requirement at diagnosis), anti-TNF biologics such as infliximab or adalimumab should be initiated as first-line therapy. 1, 2

Disease Severity Assessment

Before selecting treatment, determine disease severity using clinical symptoms, objective inflammatory markers (CRP, fecal calprotectin), endoscopic findings, and risk factors for poor prognosis. 1, 2

High-risk features indicating need for early biologic therapy include: 2

• Stricturing or penetrating disease behavior
• Perianal fistulas
• Age under 40 years at diagnosis
• Need for corticosteroids at presentation
• Extensive small bowel involvement
• Deep ulcerations on endoscopy

Treatment Algorithm by Disease Severity

Mild to Moderate Disease (Ileal/Right Colonic)

First-line: Oral budesonide 9 mg/day to induce remission 1, 2

• Evaluate response at 4-8 weeks 1
• Budesonide is preferred over prednisone for mild disease due to fewer systemic side effects 1
• Do not use budesonide for maintenance therapy 1

If budesonide fails: Escalate to prednisone 40-60 mg/day 1, 3

Mild to Moderate Disease (Colonic)

First-line: Sulfasalazine 4-6 g/day 1

• Evaluate response at 2-4 months 1
• Do not use other 5-ASA compounds - they are ineffective for Crohn's disease 1

Moderate to Severe Disease (Standard Risk)

First-line: Oral prednisone 40-60 mg/day 1, 2, 3

• Evaluate response at 2-4 weeks 1, 2
• Taper gradually over 8 weeks once remission achieved 2
• Expected remission rate: 60-83% 3

If inadequate response or steroid-dependent/resistant: Initiate anti-TNF therapy (infliximab or adalimumab) 1, 2

Moderate to Severe Disease (High Risk)

First-line: Anti-TNF biologics (infliximab or adalimumab) 1, 2

• Strong recommendation with high-quality evidence 1
• Evaluate response at 8-12 weeks 1
• Consider combination therapy with thiopurine or methotrexate to improve pharmacokinetics and reduce immunogenicity 1, 2

Severe Disease Requiring Hospitalization

Intravenous methylprednisolone 40-60 mg/day (typically 40 mg every 8 hours) 1, 2

• Evaluate response within 1 week 1, 2
• If no response, escalate to biologics or consider surgical consultation 2

Biologic Therapy Options

Anti-TNF Agents (First-Line Biologics)

Infliximab: 4

• Dosing: 5 mg/kg IV at weeks 0,2,6, then every 8 weeks
• May increase to 10 mg/kg if loss of response
• Black box warning: Serious infections (TB reactivation, invasive fungal infections) and malignancy risk, especially hepatosplenic T-cell lymphoma in young males on combination therapy with thiopurines 4

Adalimumab: Similar efficacy to infliximab 1

Alternative Biologics (After Anti-TNF Failure)

Vedolizumab: For patients failing corticosteroids, thiopurines, methotrexate, or anti-TNF therapy 2

• Gut-selective mechanism with better safety profile 2
• Evaluate response at 10-14 weeks 2

Ustekinumab: For moderate to severe disease failing other therapies 2, 5

• Initial IV dose (weight-based): 260 mg (≤55 kg), 390 mg (55-85 kg), or 520 mg (>85 kg) 5
• Maintenance: 90 mg subcutaneous every 8 weeks starting at week 8 5
• Evaluate response at 6-10 weeks 2

Maintenance Therapy

After Steroid-Induced Remission

Thiopurines (azathioprine/mercaptopurine): For selected patients achieving remission with steroids 1, 2

• Conditional recommendation with very low-quality evidence 1
• Evaluate at 12-16 weeks; modify therapy if no corticosteroid-free remission 1

Parenteral methotrexate: Alternative for steroid-dependent/resistant patients 1, 2

• Continue for maintenance if used for induction 1

After Biologic-Induced Remission

Continue the same biologic indefinitely 1, 2

• Strong recommendation with high-quality evidence 1
• If loss of response, consider dose optimization guided by therapeutic drug monitoring 1

Critical Maintenance Principle

Never use corticosteroids for maintenance therapy - they are completely ineffective and associated with significant toxicity 1, 2, 3

Therapies NOT Recommended

The following have insufficient evidence and should not be used: 2

• Systemically absorbed antibiotics (except for septic complications) 1
• Probiotics
• Omega-3 fatty acids
• Marijuana
• Naltrexone
• Enteral nutrition or dietary modification alone in adults 2

Special Considerations

Combination Therapy

When initiating anti-TNF therapy, consider adding thiopurine or methotrexate to improve pharmacokinetics and reduce immunogenicity 1, 2. However, balance this against increased infection risk, particularly hepatosplenic T-cell lymphoma in young males 4.

Pain Management

For patients with pain and comorbid depression, tricyclic antidepressants may provide dual benefits 2, 6. Avoid long-term opioid use - associated with poor outcomes in IBD 2, 6.

Monitoring

Regular objective monitoring with endoscopy, CRP, fecal calprotectin, or imaging is essential, as symptoms may not correlate with inflammation 2. Up to 50% of patients require surgery within 10 years despite medical therapy 2.

Common Pitfalls

• Using corticosteroids for maintenance (ineffective and harmful) 1, 2
• Delaying biologics in high-risk patients (leads to complications and disability) 1, 2
• Using 5-ASA compounds other than sulfasalazine (no evidence of benefit) 1
• Continuing ineffective therapy beyond appropriate evaluation timeframes 1, 2