What are the treatment options for Crohn's disease?

Treatment of Crohn's Disease

For mild-to-moderate Crohn's disease limited to the ileum and/or ascending colon, use budesonide 9 mg/day; for moderate-to-severe disease or more extensive involvement, use systemic corticosteroids (prednisolone 40-60 mg/day or IV methylprednisolone 40-60 mg/day for hospitalized patients), followed by early introduction of anti-TNF biologics with or without immunomodulators for maintenance. 1, 2, 3

Induction Therapy Based on Disease Severity

Mild-to-Moderate Disease (Ileum/Right Colon)

• Budesonide 9 mg/day is the preferred first-line agent for disease limited to the ileum and/or ascending colon due to superior efficacy over placebo (RR 1.93 for remission) and better safety profile compared to systemic steroids 1, 2
• Budesonide has high topical anti-inflammatory activity with low systemic absorption, resulting in fewer systemic side effects than conventional corticosteroids 1
• Mesalazine (5-ASA) is NOT recommended for induction of remission in Crohn's disease, as high-dose mesalazine (3-4.5 g/day) shows no superiority over placebo 2, 4

Moderate-to-Severe Disease

• Systemic corticosteroids are recommended for induction: prednisolone 0.5-0.75 mg/kg/day (maximum 60 mg/day) or methylprednisolone 48 mg/day, tapered over 8-12 weeks 1, 2
• For hospitalized patients requiring IV therapy: methylprednisolone 40-60 mg/day (typically 40 mg every 8 hours) 3
• Corticosteroids are twice as effective as placebo for inducing remission (RR 1.99), but carry 5-fold higher adverse event risk including Cushing syndrome, infections (particularly abdominal/pelvic abscesses), hypertension, diabetes, and osteoporosis 1
• Evaluate response within 2-4 weeks; if no response, modify therapy 2, 3
• Patients who do not respond by week 14 are unlikely to benefit from continued corticosteroid therapy and should be transitioned to alternative treatment 5

Critical Pitfall

Never use corticosteroids for maintenance therapy - they are only for induction and must be followed by steroid-sparing maintenance agents 2, 3

Maintenance Therapy After Achieving Remission

First-Line Maintenance Strategy

• Early introduction of anti-TNF biologics (infliximab, adalimumab) with or without immunomodulators is strongly recommended after corticosteroid-induced remission, particularly for patients with moderate-to-severe disease or risk factors for poor prognosis 2, 3
• Combination therapy with infliximab plus thiopurine is more effective than monotherapy for maintaining remission 2
• Infliximab dosing: 5 mg/kg IV at weeks 0,2, and 6, then every 8 weeks; may increase to 10 mg/kg for patients who lose response 5
• Evaluate anti-TNF response between 8-12 weeks; discontinue if no response by week 14 2

Alternative Maintenance Options

• Thiopurines (azathioprine, mercaptopurine): Consider for patients with adverse prognostic factors or to maintain corticosteroid-induced remission, though NOT recommended as monotherapy for induction 1, 2, 3
• Methotrexate: Subcutaneous administration at ≥15 mg weekly with folic acid supplementation; reserved for patients who achieved remission with methotrexate or cannot tolerate thiopurines 2, 3
• Vedolizumab: For patients who fail corticosteroids, thiopurines, methotrexate, or anti-TNF therapy; evaluate response at 10-14 weeks 3
• Ustekinumab: For moderate-to-severe disease after failure of other therapies; evaluate response at 6-10 weeks 3

Important Drug Interactions and Safety Considerations

Concomitant Immunosuppression

• Concomitant methotrexate use decreases anti-drug antibody production and increases infliximab concentrations 5
• Patients receiving immunosuppressants with infliximab experience fewer infusion reactions 5
• Avoid combination with anakinra, abatacept, or tocilizumab due to increased infection risk without added benefit 5

Infection Risk Management

• Screen for latent tuberculosis before initiating anti-TNF therapy and treat latent infection prior to starting biologics 5
• Monitor closely for invasive fungal infections (histoplasmosis, coccidioidomycosis) and opportunistic infections during treatment 5
• Most serious infections occur in patients taking concomitant immunosuppressants (methotrexate, corticosteroids) 5

Malignancy Risk

• Hepatosplenic T-cell lymphoma (HSTCL) has been reported, particularly in adolescent and young adult males receiving TNF-blockers with azathioprine or 6-mercaptopurine 5
• This rare but fatal malignancy occurs almost exclusively in patients with concomitant thiopurine use 5

Vaccination Considerations

• Do not administer live vaccines during anti-TNF therapy 5
• Infants exposed to infliximab in utero should not receive live vaccines (BCG, rotavirus) for at least 6 months after birth due to transplacental drug transfer 5

Monitoring Strategy

• Regular objective monitoring is essential using endoscopy, C-reactive protein (CRP), fecal calprotectin, and imaging, as clinical symptoms often disconnect from underlying inflammation 1, 3
• This tight control approach allows therapy adjustment to maximize disease control and prevent progressive bowel damage 1

Agents to Avoid

• Thiopurines as monotherapy for induction: Very low-quality evidence shows no benefit over placebo (RR 1.23; 95% CI 0.97-1.55) 1
• Mesalazine/5-ASA: Not effective for induction or maintenance in Crohn's disease 2, 4
• Antibiotics: Have not consistently demonstrated efficacy for luminal Crohn's disease 2
• Long-term opioids: Associated with poor outcomes in IBD patients 3
• Probiotics, omega-3 fatty acids, marijuana, naltrexone: Not recommended for inducing or maintaining remission 3