What are the current treatment guidelines for Crohn’s disease?

Current Treatment Guidelines for Crohn's Disease

Biologic therapy with or without immunomodulators is recommended as the most effective treatment strategy for moderate to severe Crohn's disease, rather than delaying their use until after failure of mesalamine and/or corticosteroids. 1

Disease Classification and Initial Treatment Approach

Mild-to-Moderate Disease

• For mild-to-moderate ileal/ileocolonic disease:

  • Budesonide 9 mg daily for 8 weeks is strongly recommended 2, 1
  • Budesonide has high topical anti-inflammatory activity and low systemic absorption, providing a better safety profile than conventional steroids 2

• For mild colonic disease:

  • Sulfasalazine 4 g daily may be considered 1
  • 5-ASA compounds are generally not recommended for Crohn's disease 2, 3

Moderate-to-Severe Disease

• First-line therapy:

  • TNF-α inhibitors (infliximab, adalimumab, certolizumab pegol) with or without immunomodulators 1, 4
  • For Crohn's disease, adalimumab dosing: 160 mg on Day 1,80 mg on Day 15, then 40 mg every other week starting on Day 29 4

• Alternative biologics:

  • IL-12/23 inhibitors (ustekinumab) for patients with inadequate response to TNF inhibitors or as first-line in selected patients 1
  • Anti-integrin agents (vedolizumab) for patients with inadequate response to TNF inhibitors or as first-line in selected patients 1, 5
  • Vedolizumab dosing: 300 mg IV at weeks 0,2, and 6, then every 8 weeks; or 108 mg subcutaneously every 2 weeks after initial IV induction 5

Corticosteroids

• Systemic corticosteroids:

  • Recommended for short-term induction of remission in moderate-to-severe disease 2, 1
  • Prednisolone 40-60 mg daily, tapered at 5 mg/week over 8-12 weeks 2, 1
  • Not suitable for maintenance therapy due to significant side effects 2, 1
  • Side effects include Cushing syndrome, acne, increased infection risk, hypertension, diabetes, osteoporosis, cataracts, and glaucoma 2

• Budesonide:

  • Superior to placebo for inducing clinical response (RR: 1.46; 95% CI: 1.03-2.07) and clinical remission (RR: 1.93; 95% CI: 1.37-2.73) 2
  • Not superior to mesalamine for inducing clinical remission (RR: 1.30; 95% CI: 0.98-1.72) but better for clinical response 2

Maintenance Therapy

• Immunomodulators:

  • Thiopurines (azathioprine 1.5-2.5 mg/kg/day or 6-mercaptopurine 0.75-1.5 mg/kg/day) are recommended for steroid-dependent patients 1
  • Methotrexate (15-25 mg weekly, preferably parenteral) is an alternative for patients who cannot tolerate thiopurines 1

• Biologics:

  • Continue the biologic that induced remission 1
  • Combination therapy with a TNF inhibitor and an immunomodulator improves efficacy and reduces immunogenicity 1

Special Considerations

Perianal Fistulizing Disease

• Infliximab is strongly recommended, with adalimumab, ustekinumab, or vedolizumab as alternatives 1
• Combination therapy with antibiotics is recommended for induction of fistula remission 1

High-Risk Patients

• Early biological therapy, potentially combined with immunomodulators, is recommended for patients with extensive disease or poor prognostic factors 1

Monitoring and Follow-up

• Regular assessment of disease activity using objective markers (endoscopy, CRP, fecal calprotectin) is essential 1
• Laboratory monitoring specific to each medication and screening for tuberculosis before initiating biologic therapy 1, 5, 4
• Discontinue therapy if no evidence of therapeutic benefit by Week 14 5

Important Caveats and Pitfalls

• 5-ASA compounds are not recommended for Crohn's disease despite their common use 2, 3
• Avoid prolonged corticosteroid use without a steroid-sparing strategy 1
• Antibiotics are not recommended for luminal disease outside of septic complications 2, 1
• Smoking cessation is strongly recommended as smoking worsens Crohn's disease 1
• Prophylactic calcium and vitamin D should be used to prevent osteoporosis in patients on corticosteroids 1

The treatment approach should be guided by disease location, activity, severity, previous response to therapy, and presence of complications, with regular monitoring to adjust therapy as needed to achieve tight control of inflammation 2.