What is the initial treatment approach for a patient with moderate Crohn's (inflammatory bowel) disease?

Initial Treatment for Moderate Crohn's Disease

For patients with moderate Crohn's disease, oral corticosteroids such as prednisolone 40-60 mg daily should be initiated as first-line therapy, with consideration for early addition of thiopurines (azathioprine 1.5-2.5 mg/kg/day) or biologic therapy (infliximab) to maintain remission and minimize steroid exposure. 1

Treatment Algorithm Based on Disease Location and Severity

For Moderate Ileocolonic or Ileal Disease:

• Start with oral prednisolone 40 mg daily for patients with moderate disease activity or those who failed high-dose mesalazine 1
• Prednisolone should be tapered gradually over 8 weeks based on patient response; more rapid reduction increases early relapse risk 1
• For isolated ileo-caecal disease, budesonide 9 mg daily is an alternative option, though marginally less effective than prednisolone 1
• Evaluate symptomatic response between 2-4 weeks to determine need for therapy modification 1

For Moderate Colonic Disease:

• Oral prednisolone 40-60 mg daily remains the recommended first-line therapy 1
• Sulfasalazine 4 g daily may be considered for colonic disease in selected patients, though it has high side effect rates and is not first-line 1

Critical Pitfall: Mesalazine Should NOT Be Used

The AGA strongly recommends against using mesalazine (5-ASA) for induction or maintenance of remission in Crohn's disease of any severity 1. This represents a major shift from older practice patterns:

• Multiple meta-analyses and systematic reviews demonstrate no efficacy over placebo 1
• Even high-dose mesalazine (4 g/daily) shows no clear benefit for moderate disease 1
• This applies regardless of disease location, including colonic Crohn's disease 1

Early Introduction of Maintenance Therapy

The most important contemporary recommendation is early introduction of steroid-sparing agents rather than waiting for steroid failure 1:

• For patients responding to prednisolone, introduce thiopurines (azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day) early to minimize relapse risk as steroids are withdrawn 1
• Alternative: methotrexate 15-25 mg weekly (subcutaneous preferred) for steroid-sparing 1
• Consider early biologic therapy (infliximab or adalimumab) with or without immunomodulator rather than delaying until after conventional therapy failure 1

Evidence for Early Combination Therapy:

• Early combination therapy with infliximab plus azathioprine achieves 61.5% corticosteroid-free remission at 52 weeks versus 42.2% with step-up therapy 1
• Combination infliximab with thiopurine is more effective than infliximab monotherapy for both induction and maintenance 1
• The REACT trial showed lower rates of major adverse complications at 24 months with early combination therapy 1

Biologic Therapy Considerations

For moderate to severe disease with poor prognostic factors, anti-TNF therapy should be considered as first-line treatment 1:

• Infliximab 5 mg/kg at weeks 0,2, and 6, then every 8 weeks is the standard induction and maintenance regimen 1, 2
• For patients losing response, dose escalation to 10 mg/kg may be considered 2
• Combination with thiopurine reduces immunogenicity and improves outcomes 1
• Patients who don't respond by week 14 are unlikely to benefit from continued dosing 2

Adjunctive Therapies

• Azathioprine or mercaptopurine can be used as adjunctive therapy during active disease, but slow onset of action (3-4 months) precludes use as sole therapy 1
• Nutritional support (enteral or parenteral) is appropriate if patient is malnourished 1
• Elemental or polymeric diets are less effective than corticosteroids but may be used in patients with contraindications to steroids 1

What NOT to Use for Moderate Disease

Strong recommendations against:

• Corticosteroids for maintenance therapy - associated with significant adverse effects without efficacy 1
• Mesalazine/5-ASA for any indication in Crohn's disease 1
• Thiopurine monotherapy for induction - too slow acting 1
• Antibiotics as monotherapy (metronidazole, ciprofloxacin) - not recommended first-line due to side effects, though may have role in selected patients 1

Monitoring and Response Assessment

• Evaluate response to prednisolone at 2-4 weeks 1
• If no response or inadequate response, escalate to biologic therapy rather than continuing ineffective treatment 1
• For patients on thiopurines or methotrexate who don't achieve corticosteroid-free remission within 12-16 weeks, modify therapy 1