What are the treatment options for Crohn's disease?

Treatment Options for Crohn's Disease

The treatment of Crohn's disease should follow a step-wise approach based on disease severity, location, and individual risk factors, with biologics (TNF inhibitors) and immunomodulators recommended for moderate-to-severe disease to improve mortality and quality of life outcomes. 1

First-Line Treatment Based on Disease Severity

Mild to Moderate Disease

• For mild to moderate disease limited to the ileum and/or ascending colon, budesonide 9 mg/day is recommended as first-line therapy due to its better safety profile compared to systemic corticosteroids 2, 1
• Budesonide is 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) with fewer systemic side effects than conventional steroids 2
• 5-ASA compounds (mesalazine) are not recommended for induction of remission in Crohn's disease (RR: 1.28; 95% CI: 0.97–1.69) 2, 1
• Sulfasalazine may have modest efficacy when Crohn's disease is confined to the colon 3
• Antibiotics have not consistently demonstrated efficacy for luminal Crohn's disease and should only be used when septic complications are suspected 1, 4

Moderate to Severe Disease

• Systemic corticosteroids (prednisolone 40-60 mg/day) are recommended for induction of remission in moderate-to-severe Crohn's disease 2, 1
• Corticosteroids are twice as effective as placebo in inducing clinical remission (RR: 1.99; 95% CI: 1.51–2.64) but have significant adverse effects 2
• Response to corticosteroids should be evaluated within 2-4 weeks, with consideration of alternative therapies if inadequate response 1

Maintenance Therapy

• Thiopurines (azathioprine, mercaptopurine) are not recommended as monotherapy for induction of remission but are effective for maintaining remission after corticosteroid-induced response 2, 1
• Early introduction of biologics (TNF inhibitors) with or without immunomodulators is recommended after achieving remission with corticosteroids 1
• Infliximab is FDA-approved for reducing signs and symptoms, inducing and maintaining clinical remission in moderate to severe Crohn's disease patients who have had inadequate response to conventional therapy 5
• Combination therapy with infliximab and a thiopurine is more effective than monotherapy for maintaining remission 1
• Methotrexate (at least 15 mg weekly subcutaneously with folic acid supplementation) is another option for maintenance therapy 1

Treatment Strategies

Step-Up vs. Top-Down Approach

• Traditional step-up approach involves progressively increasing therapy intensity with disease severity 4
• Top-down strategy uses biologics with immunomodulators as first-line therapy 6
• Early use of biologic therapy in combination with immunomodulators has shown faster remission, longer time to relapse, decreased need for corticosteroids, and improved mucosal healing 6
• The European Crohn's and Colitis Organisation (ECCO) currently recommends a stratified approach based on prognostic risk factors 2

Special Considerations

• Approximately 20-30% of patients with Crohn's disease have a mild disease course and may not require aggressive immunosuppression 7
• Patients who do not respond to infliximab by week 14 are unlikely to respond with continued dosing and should be considered for alternative therapy 5
• For patients with fistulizing Crohn's disease, infliximab is indicated for reducing draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure 5
• Regular monitoring using objective markers (endoscopy, C-reactive protein, calprotectin, imaging) is crucial to assess disease activity and guide therapy adjustments 2

Potential Risks and Monitoring

• Patients on TNF inhibitors have increased risk of serious infections that may lead to hospitalization or death 5
• Lymphoma and other malignancies have been reported in patients treated with TNF blockers, particularly when used with thiopurines 5
• Patients should be tested for latent tuberculosis before and during therapy with biologics 5
• Invasive fungal infections can occur and may present with disseminated rather than localized disease 5

Treatment Algorithm

1. Assess disease severity, location, and risk factors for progression
2. For mild-moderate disease limited to ileum/right colon: Start with budesonide 9 mg/day 2, 1
3. For moderate-severe or extensive disease: Use systemic corticosteroids 2, 1
4. Evaluate response within 2-4 weeks 1
5. For responders: Initiate maintenance therapy with immunomodulators or biologics 1
6. For non-responders: Consider early introduction of biologics (TNF inhibitors) with or without immunomodulators 1, 5
7. Monitor disease activity regularly using objective markers and adjust therapy accordingly 2