Initial Treatment for Crohn's Disease
For newly diagnosed Crohn's disease, treatment should be stratified by disease severity and location: mild ileocaecal disease starts with budesonide 9 mg daily for up to 12 weeks, mild colonic disease with sulfasalazine 4-6 g/day, and moderate-to-severe disease requires early biologic therapy (infliximab or adalimumab) with or without immunomodulators. 1, 2
Disease Severity Stratification
Treatment selection depends critically on assessing disease severity using clinical symptoms, objective inflammatory markers (faecal calprotectin), endoscopic findings, and risk factors for progression 2. This initial assessment determines whether to pursue a conservative approach or early advanced therapy.
Mild Ileocaecal or Right-Sided Ileocolonic Disease
Budesonide 9 mg daily is the first-line therapy for mild ileal or ileocolonic Crohn's disease 1. This controlled ileal-release corticosteroid is as effective as conventional corticosteroids for inducing clinical remission but with significantly fewer adverse events 1. Treatment duration should not exceed 12 weeks 1.
- Evaluate symptomatic response between 4-8 weeks to determine need for therapy modification 1, 2
- Budesonide has better tolerability than systemic corticosteroids with less adrenal suppression 1
- Early assessment at 2 weeks with clinical and/or biomarker (faecal calprotectin) response is recommended to enable timely escalation if needed 1
Important caveat: Budesonide is ineffective for maintenance therapy and should not be continued beyond the induction period 1.
Mild Colonic Disease
Sulfasalazine 4-6 g/day is recommended for mild Crohn's disease limited to the colon 1, 2. This represents the only aminosalicylate with demonstrated modest efficacy in Crohn's disease, specifically when disease is confined to the colon 1.
- Evaluate symptomatic response between 2-4 months to determine need for therapy modification 1, 2
- Sulfasalazine is inferior to corticosteroids but has fewer adverse events 3
- Patients who respond may continue on sulfasalazine for maintenance 1
Critical distinction: Other mesalamine formulations (including high-dose preparations up to 4.5 g/day) are NOT recommended for Crohn's disease as they show no significant benefit over placebo 1, 3.
Moderate-to-Severe Disease
Early biologic therapy with anti-TNF agents (infliximab or adalimumab) is strongly recommended as first-line treatment for moderate-to-severe Crohn's disease, particularly in patients with risk factors for poor prognosis 1, 2. This represents a paradigm shift from traditional step-up approaches.
Anti-TNF Induction Regimens
Infliximab: 5 mg/kg intravenous at weeks 0,2, and 6 1, 4
Adalimumab: 160 mg subcutaneous on Day 1 (single dose or split over two consecutive days), followed by 80 mg at Day 15, then 40 mg every other week starting Day 29 1, 4
Combination Therapy
Combination therapy of infliximab with a thiopurine (azathioprine) is more effective than monotherapy for induction and maintenance of remission 1. The landmark SONIC study demonstrated superiority of combination therapy for achieving clinical remission and mucosal healing 1.
- Combination therapy reduces immunogenicity risk (HR 0.37, p<0.0001) 1
- Combination therapy reduces need for dose escalation and drug switching 1
- For adalimumab, combination with thiopurine or methotrexate improves pharmacokinetic parameters 1
Important consideration: While combination therapy increases infection risk, the benefits in moderate-to-severe disease typically outweigh risks 2.
Response Assessment
Evaluate symptomatic response to anti-TNF induction therapy between 8-12 weeks to determine need for therapy modification 1. At week 2 after initial infliximab infusion, approximately 58% of patients respond 1.
Systemic Corticosteroids for Moderate-to-Severe Disease
Systemic corticosteroids are suggested for induction of remission in moderate-to-severe Crohn's disease when biologics are not immediately available or appropriate, but should be limited to no longer than 8 weeks 1.
- For hospitalized patients with severe disease: intravenous methylprednisolone 40-60 mg/day 1
- Evaluate response within 1 week to determine need for therapy modification 1
- Whenever prescribing systemic corticosteroids, consider whether initiation or change of advanced therapy is required 1
- Repeated courses of steroids should be avoided unless futility of other effective therapies has been established 1
Critical warning: Corticosteroids are NOT recommended for maintenance of remission in Crohn's disease 1.
Maintenance Therapy After Corticosteroid-Induced Remission
For patients achieving remission on corticosteroids who are not on biologics, early introduction of maintenance therapy with thiopurines (azathioprine or 6-mercaptopurine) or methotrexate should be considered to minimize risk of flare as corticosteroids are withdrawn 1.
- Thiopurines have slow onset of action (3-6 months) 2
- Methotrexate dose should be at least 15 mg weekly, with subcutaneous administration having better bioavailability than oral 1
- Evaluate for corticosteroid-free remission within 12-16 weeks; if not achieved, therapy should be modified 1
What NOT to Use
Mesalamine (5-ASA) formulations are not recommended for induction or maintenance treatment of Crohn's disease 1. Multiple high-quality studies and meta-analyses demonstrate no significant benefit over placebo, even at high doses (4-4.5 g/day) 1, 3.
Common Pitfalls to Avoid
Delaying biologic therapy in moderate-to-severe disease by using a step-up approach with mesalamine or corticosteroids first may result in clinical harm from disease progression 2
Using corticosteroids for maintenance leads to steroid dependence and does not prevent disease progression 1
Prescribing mesalamine for any severity of Crohn's disease wastes resources without clinical benefit 1
Failing to assess early response (2 weeks for steroids, 8-12 weeks for biologics) delays appropriate therapy escalation 1
Using budesonide beyond 12 weeks as it is ineffective for maintenance 1