What are the treatment options for managing Crohn's disease?

Management of Crohn's Disease

For moderate to severe Crohn's disease, initiate systemic corticosteroids (prednisolone 40-60 mg/day or IV methylprednisolone 40-60 mg/day for hospitalized patients) as first-line therapy, but strongly consider early introduction of biologic therapy (anti-TNF agents, vedolizumab, or ustekinumab) in patients with high-risk features including complex disease at presentation, perianal fistulizing disease, age under 40 years, or need for steroids to control the index flare. 1, 2, 3

Initial Treatment Strategy by Disease Severity

Mild to Moderate Disease

• For ileocecal disease specifically, start with oral budesonide 9 mg/day as it has fewer systemic side effects than conventional corticosteroids 1, 3
• If budesonide is ineffective or disease extends beyond ileocecal region, escalate to prednisolone 40-60 mg/day 1, 3
• Do NOT use 5-aminosalicylate (5-ASA) compounds for induction or maintenance therapy—they are ineffective at doses <2 g/day and show no benefit even at higher doses in moderate disease 1, 2

Moderate to Severe Disease

• Initiate prednisolone 40-60 mg/day orally, or IV methylprednisolone 40-60 mg/day if hospitalized 1, 3
• Evaluate response at 2-4 weeks; if inadequate response, modify therapy 3
• Taper steroids gradually over 8 weeks once remission achieved—faster tapering increases relapse risk 3
• Critical caveat: Assess for high-risk features that warrant early biologic therapy rather than conventional step-up approach 1, 2

High-Risk Disease Requiring Early Biologics

Consider immediate biologic therapy (bypassing conventional step-up) for patients with: 1, 2

• Complex disease behavior (stricturing or penetrating) at presentation
• Perianal fistulizing disease
• Age <40 years at diagnosis
• Extensive disease burden
• Need for steroids to control initial presentation

The REACT trial demonstrated that early combined immunosuppression with anti-TNF agents in high-risk patients significantly reduced complications, hospitalizations, and surgeries compared to conventional management. 2

Biologic Therapy Selection

First-Line Biologic Options

All three classes can be considered as first-line biologics: 1, 2

Anti-TNF agents (infliximab, adalimumab, certolizumab):

• Infliximab: 5 mg/kg IV at weeks 0,2,6, then every 8 weeks 4
• Adalimumab: 160 mg SC day 1 (single dose or split over 2 days), 80 mg day 15, then 40 mg every other week starting day 29 5
• For infliximab specifically, combine with thiopurine (azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day) to improve response rates and reduce immunogenicity 2

Vedolizumab: For patients preferring gut-selective therapy or those with contraindications to anti-TNF agents; evaluate response at 10-14 weeks 3

Ustekinumab: Particularly useful after anti-TNF failure; evaluate response at 6-10 weeks 2, 3

Important Safety Consideration

Combination therapy with anti-TNF agents plus thiopurines carries increased risk of hepatosplenic T-cell lymphoma (HSTCL), particularly in adolescent and young adult males with inflammatory bowel disease. 4, 5 This rare but fatal malignancy should be discussed when considering combination therapy, especially in male patients.

Maintenance Therapy

What NOT to Use

• Never use corticosteroids (systemic or budesonide) for maintenance—they are ineffective and toxic for long-term use 1, 2
• Avoid 5-ASA compounds—insufficient efficacy for maintenance 1

Effective Maintenance Options

Thiopurines (azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day): 1, 2

• Effective as monotherapy for maintenance
• Reserved as second-line due to toxicity concerns
• Mandatory: Check TPMT activity before initiating; do not use if deficient, reduce dose if below normal 1
• Indicated when: two or more exacerbations in 12 months, inability to taper steroids, or used with steroids to induce remission

Methotrexate (15-25 mg IM/SC weekly): 1

• Use only if patient responded to methotrexate for induction
• Alternative for patients intolerant of or failed by thiopurines
• Add folic acid 5 mg once weekly, 3 days after methotrexate dose 1

Biologic continuation: 2, 3

• Patients responding to biologic induction should continue the same agent for maintenance
• Infliximab: 5-10 mg/kg every 8 weeks 1, 4
• Adalimumab: 40 mg every other week 5
• Assess for mucosal healing within 1 year of treatment initiation 1

Fistulizing and Perianal Disease

This requires combined medical-surgical approach: 1

First-line antibiotics:

• Metronidazole 400 mg three times daily AND/OR
• Ciprofloxacin 500 mg twice daily

For refractory fistulae:

• Infliximab (5 mg/kg at weeks 0,2,6) combined with immunomodulators and surgical drainage 1
• MRI and examination under anesthesia to define anatomy and exclude abscess before medical therapy 1
• Surgical options include Seton drainage, fistulectomy, or advancement flaps in combination with medical treatment 1

Monitoring and Treatment Adjustment

• Evaluate steroid response at 2-4 weeks; modify therapy if inadequate 3
• For patients losing response to infliximab 5 mg/kg, consider increasing to 10 mg/kg 1, 4
• Patients not responding by week 14 are unlikely to benefit from continued therapy—discontinue and consider alternatives 4
• Monitor with objective markers (endoscopy, CRP, fecal calprotectin, imaging) as symptoms poorly correlate with inflammation 3

Critical Pitfalls to Avoid

1. Do not use thiopurines or methotrexate as monotherapy for induction—they are too slow-acting 1
2. Avoid long-term opioid use—associated with poor outcomes in IBD 3
3. Do not continue ineffective therapy—reassess by week 14 for biologics 4
4. Screen for latent tuberculosis before starting any biologic—treat latent TB before initiating anti-TNF therapy 4, 5
5. Smoking cessation is mandatory—probably the most important factor in maintaining remission 1