What is the treatment for moderate Crohn's disease?

Treatment of Moderate Crohn's Disease

For moderate Crohn's disease, biologic therapy with or without an immunomodulator is recommended as the most effective treatment strategy, rather than delaying their use until after failure of mesalamine and/or corticosteroids. 1

Definition of Moderate Crohn's Disease

Moderate Crohn's disease is typically defined as:

• CDAI score of 220-450 1
• Symptoms that impact daily activities but do not require hospitalization
• May include:
  • Frequent loose stools (but less than 10 per day)
  • Mild to moderate abdominal pain
  • Weight loss less than 10%
  • No signs of obstruction, fever, dehydration, or abdominal mass

First-Line Treatment Options

Biologic Agents

1. TNF-α Inhibitors:

   • Infliximab: 5 mg/kg IV at weeks 0,2, and 6, then every 8 weeks 1, 2
   • Adalimumab: 160 mg initially, 80 mg at week 2, then 40 mg every other week 3
   • Certolizumab pegol: Available in some regions (not approved in EU) 1

2. IL-12/23 Inhibitor:

   • Ustekinumab: Weight-based IV induction dose (approximately 6 mg/kg), followed by SC maintenance 1

3. Anti-integrin Agent:

   • Vedolizumab: For patients with inadequate response to TNF inhibitors or as first-line in selected patients 1, 4

Combination Therapy

• TNF inhibitor + thiopurine: Recommended particularly for infliximab to improve efficacy and reduce immunogenicity 1
  • Example: Infliximab + azathioprine (1.5-2.5 mg/kg/day) 4

Corticosteroids

• Short-term use only: Effective for induction of remission but not maintenance 1
• Budesonide: 9 mg daily for 8 weeks (for ileal/ileocolonic disease) 4
• Systemic corticosteroids: Prednisolone 40-60 mg daily with taper (for more severe symptoms) 4

Treatment Algorithm for Moderate Crohn's Disease

1. Initial Assessment:

   • Confirm disease activity with objective markers (endoscopy, CRP, fecal calprotectin)
   • Assess disease location (ileal, colonic, ileocolonic)
   • Rule out complications (strictures, fistulas, abscesses)

2. First-line Therapy:

   • Preferred approach: Early introduction of biologic therapy (TNF inhibitor) with or without an immunomodulator 1
   • For ileal/right-sided disease: Consider budesonide 9 mg daily for induction 4

3. If Primary Non-response to TNF inhibitor:

   • Switch to ustekinumab (recommended) or vedolizumab (suggested) 1

4. If Secondary Non-response to TNF inhibitor:

   • If initial response to infliximab then loss of response: Switch to adalimumab or ustekinumab 1
   • If initial response to adalimumab then loss of response: Consider switching to infliximab 1

5. Maintenance Therapy:

   • Continue the biologic that induced remission 4
   • If biologic + immunomodulator combination was used, no clear recommendation on withdrawal of either agent exists 1

Important Considerations

Treatments to Avoid

• 5-ASA compounds: Not recommended for induction or maintenance of remission in moderate Crohn's disease 1, 4
• Corticosteroids for maintenance: Strong recommendation against this practice due to significant side effects 1, 4
• Antibiotics alone: Not effective for luminal disease outside of septic complications 4

Special Situations

• Perianal Fistulizing Disease:
  • Infliximab is strongly recommended (most robust evidence) 1
  • Adalimumab, ustekinumab, or vedolizumab are suggested alternatives 1
  • Combination with antibiotics is recommended for induction of fistula remission 1

Monitoring

• Regular assessment of disease activity using objective markers
• Laboratory monitoring specific to each medication
• Screening for tuberculosis and other infections before initiating biologic therapy
• Monitoring for drug-specific adverse effects

Common Pitfalls to Avoid

• Delaying biologic therapy in moderate disease
• Using 5-ASA compounds which lack efficacy in moderate Crohn's disease
• Prolonged corticosteroid use without a steroid-sparing strategy
• Failing to monitor for medication side effects
• Not considering disease location when selecting therapy

By following this evidence-based approach to treating moderate Crohn's disease, patients are more likely to achieve clinical remission, mucosal healing, and improved quality of life with minimized risks of disease progression and complications.