Initial Treatment of Crohn's Disease
For newly diagnosed Crohn's disease, treatment should be stratified by disease severity and location: budesonide 9 mg daily for mild ileocecal disease, sulfasalazine for mild colonic disease, and early anti-TNF biologic therapy (infliximab or adalimumab) for moderate-to-severe disease with poor prognostic factors. 1
Disease Severity Stratification
Before initiating therapy, determine disease severity using clinical symptoms, objective inflammatory markers (CRP, fecal calprotectin), endoscopic findings, and risk factors for progression 1. This assessment dictates the treatment pathway and urgency of intervention.
Mild Disease (Ileocecal Location)
Budesonide 9 mg daily is the first-line treatment for mild Crohn's disease limited to the ileum and/or ascending colon 2. This controlled-release corticosteroid provides:
- Superior efficacy to placebo for inducing clinical remission (RR 1.93; 95% CI 1.37-2.73) 2
- Comparable efficacy to conventional corticosteroids with significantly fewer adverse effects (RR 0.64; 95% CI 0.54-0.76) 2
- High topical anti-inflammatory activity with minimal systemic absorption 2
Evaluate symptomatic response at 4-8 weeks 1. Treatment duration should not exceed 12 weeks 2. If no response by 8 weeks, escalate therapy immediately 2.
Important Caveat
Budesonide is ineffective for maintenance therapy and should not be continued beyond the induction period 2.
Mild Disease (Colonic Location)
For mild Crohn's disease limited to the colon, sulfasalazine 4-6 g/day is recommended as first-line therapy 2, 1. Evidence shows:
- Modest efficacy over placebo (RR 1.38; 95% CI 1.02-1.87) with benefit confined to colonic disease 2, 3
- Evaluate symptomatic response at 2-4 months 2
What NOT to Use
5-aminosalicylates (mesalamine) are NOT recommended for Crohn's disease 2. Multiple high-quality studies demonstrate:
- No significant benefit over placebo for induction of remission (RR 1.27; 95% CI 0.79-2.03) 2
- High-dose mesalamine (3-4.5 g/day) shows no superiority to placebo 3
- Inferior to budesonide for inducing remission 2, 3
Moderate-to-Severe Disease
For moderate-to-severe Crohn's disease, particularly with poor prognostic factors, initiate anti-TNF biologic therapy (infliximab or adalimumab) as first-line treatment 2, 1. This represents a paradigm shift from traditional step-up approaches.
Anti-TNF Induction Regimens
Infliximab: 5 mg/kg IV at weeks 0,2, and 6 2, 4
Adalimumab: 160 mg subcutaneous on Day 1 (single dose or split over two days), 80 mg at Day 15, then 40 mg every other week starting Day 29 4
Combination Therapy
Combine anti-TNF therapy with a thiopurine (azathioprine) for superior outcomes 2. The landmark SONIC study demonstrated:
- Combination infliximab plus azathioprine superior to infliximab monotherapy for clinical remission and mucosal healing 2
- Reduced immunogenicity (HR 0.37, p<0.0001) 2
- Reduced need for dose escalation and drug switching 2
Evaluate response to anti-TNF induction at 8-12 weeks 2. If suboptimal response, consider dose intensification 2.
Alternative: Methotrexate
For patients intolerant of thiopurines, parenteral methotrexate (at least 15 mg weekly, preferably subcutaneous) can be combined with anti-TNF therapy 2. However, one study showed methotrexate combination was no more effective than infliximab monotherapy at 50 weeks, though it may reduce immunogenicity 2.
Severe Disease Requiring Hospitalization
For severe Crohn's disease requiring hospitalization, use intravenous methylprednisolone 40-60 mg/day 2. Evaluate response within 1 week 2. If inadequate response, immediately consider anti-TNF therapy or surgical consultation.
Maintenance Strategy After Corticosteroid-Induced Remission
For patients achieving remission on corticosteroids, early introduction of maintenance therapy with thiopurines or methotrexate is recommended to minimize flare risk during steroid withdrawal 2, 1. Key points:
- Thiopurines have slow onset (3-6 months) 1
- Assess for corticosteroid-free remission at 12-16 weeks; if not achieved, modify therapy 2
- Never use corticosteroids for maintenance therapy 2
Critical Pitfalls to Avoid
Do not delay biologic therapy in moderate-to-severe disease by attempting a step-up approach with mesalamine or prolonged corticosteroids—this may result in clinical harm from disease progression 1
Do not use systemic corticosteroids beyond 8 weeks 2. Assess response at 2 weeks with clinical and biomarker evaluation (fecal calprotectin) to enable timely escalation 2
Do not use mesalamine for any indication in Crohn's disease—it lacks efficacy and wastes time 2
Do not continue budesonide beyond 12 weeks—it is ineffective for maintenance 2
Whenever prescribing corticosteroids, simultaneously consider whether advanced therapy initiation or change is required 2