What are the treatment options and medications for a patient with Crohn's disease?

Medication for Crohn's Disease

First-Line Therapy for Active Disease

For patients with a first presentation or single inflammatory exacerbation of Crohn's disease, conventional glucocorticosteroids (prednisolone 40-60 mg/day or methylprednisolone) are the recommended first-line therapy to induce remission. 1, 2

Disease Severity-Based Approach

Mild to Moderate Disease:

• Conventional corticosteroids (prednisone 40-60 mg/day for 2-4 weeks) are first-line for most patients 1, 2
• Budesonide is an alternative for distal ileal, ileocaecal, or right-sided colonic disease in patients who decline or cannot tolerate conventional corticosteroids 1, 2
• Sulfasalazine 4-6 g/day may be used specifically for mild colonic Crohn's disease 1
• Enteral nutrition should be considered as an alternative to corticosteroids in children and young people with growth concerns 1, 2

Moderate to Severe Disease:

• Initiate biologic therapy (TNF inhibitors) combined with thiopurine or methotrexate plus corticosteroids for high-risk patients 1, 2
• High-risk features include: early age of onset, perianal disease, corticosteroid use at presentation, and severe presentations 1

Maintenance Therapy

After achieving remission with corticosteroids, azathioprine or mercaptopurine should be offered as monotherapy to maintain remission. 1, 2

Immunosuppressive Options

• Azathioprine or mercaptopurine are first-line maintenance agents, particularly for patients with adverse prognostic factors 1, 2
• Check thiopurine methyltransferase (TPMT) activity before initiating azathioprine or mercaptopurine 1, 2
• Monitor for neutropenia even with normal TPMT activity 1, 2
• Methotrexate 25 mg/week subcutaneous or intramuscular is an alternative for patients who cannot tolerate thiopurines or have deficient TPMT activity 1, 2

When to Escalate Therapy

Add azathioprine or mercaptopurine to corticosteroids if:

• Two or more inflammatory exacerbations occur in a 12-month period 2
• The corticosteroid dose cannot be tapered (steroid-dependent disease) 2

Biologic Therapy

TNF Inhibitors (First-Line Biologics)

For moderate-to-severe Crohn's disease not responding to conventional therapy, TNF inhibitors are strongly recommended. 2, 3

Infliximab:

• Induction: 5 mg/kg IV at weeks 0,2, and 6 4
• Strongly recommend combination therapy with thiopurines to prevent antibody formation 4
• Evaluate response at weeks 8-12 4

Adalimumab: 5

• Adults: 160 mg Day 1 (single dose or split over 2 days), 80 mg Day 15, then 40 mg every other week starting Day 29
• Pediatric ≥40 kg: Same as adult dosing
• Pediatric 17-40 kg: 80 mg Day 1,40 mg Day 15, then 20 mg every other week
• High-certainty evidence shows 59% of adalimumab patients failed to maintain remission at 52-56 weeks versus 86% with placebo 6

Certolizumab pegol is FDA-approved but not licensed in Canada or Europe 1

IL-23 Inhibitors (Second-Line After TNF Failure)

Ustekinumab:

• Strongly recommended for patients with inadequate response to conventional therapy and/or anti-TNF therapy 2, 3
• Induction: ~6 mg/kg IV weight-based dosing 3
• Maintenance: subcutaneous dosing 3
• Relative risk of remission 1.76 (95% CI: 1.40-2.22) versus placebo 3

Risankizumab:

• Recommended after failure of TNF inhibitors with moderate certainty for moderate benefit 3
• Appropriate for patients who have failed two different biologic classes 3

Integrin Inhibitors

Vedolizumab:

• Evaluate response between 10-14 weeks 3
• If inadequate response after switching from anti-TNF, switch to IL-23 inhibitor rather than another anti-integrin 3

Medications NOT Recommended

Systemically absorbed antibiotics are NOT recommended for induction or maintenance of remission in luminal Crohn's disease (conditional recommendation, very low to low-quality evidence). 1 They may have a role in perianal fistulizing disease but not for standard luminal disease management.

Corticosteroids should NOT be used for maintenance of remission due to long-term toxicity and lack of efficacy. 2, 3

5-aminosalicylates (other than sulfasalazine for colonic disease) have no established role in Crohn's disease treatment. 7

Treatment Algorithm Summary

1. First exacerbation: Conventional corticosteroids → taper over 8-12 weeks 1, 2
2. Assess risk factors: If high-risk features present, add thiopurine or initiate biologic therapy 1
3. Steroid-dependent or ≥2 exacerbations/year: Add azathioprine/mercaptopurine or escalate to biologic 1, 2
4. Conventional therapy failure: TNF inhibitor (infliximab or adalimumab) with thiopurine 2, 4
5. TNF inhibitor failure: Switch to IL-23 inhibitor (ustekinumab or risankizumab) 3

Critical Monitoring Requirements

• Pre-biologic screening: Test for latent tuberculosis before initiating any biologic therapy 5
• TPMT testing: Required before azathioprine or mercaptopurine 1, 2
• Neutropenia monitoring: Continue even with normal TPMT 1, 2
• Liver function: Required before initiating risankizumab 3
• Avoid live vaccines during IL-23 inhibitor treatment 3

Common Pitfalls to Avoid

• Do not use corticosteroids beyond induction – they are ineffective and toxic for maintenance 2, 3
• Do not delay combination therapy – starting thiopurines with infliximab is more effective than adding later 4
• Do not wait for "complete failure" – steroid-dependent pattern already constitutes treatment failure requiring escalation 3
• Do not switch to another TNF inhibitor after adalimumab failure – switching to a different mechanism (IL-23 inhibitor) is more effective 3