What is the recommended treatment for a Crohn's disease flare?

Treatment of Crohn's Disease Flare

For a moderate-to-severe Crohn's disease flare, initiate anti-TNF therapy (infliximab or adalimumab) as first-line treatment, preferably in combination with a thiopurine or methotrexate, rather than using corticosteroids alone. 1, 2

First-Line Treatment: Anti-TNF Biologics

The 2024 ECCO guidelines emphasize early aggressive treatment over traditional step-up approaches. 1 The landmark PROFILE trial demonstrated that "top-down" combination therapy with IV infliximab plus immunomodulator achieved sustained steroid- and surgery-free remission in 79% of patients versus only 15% with traditional step-up care (p < 0.001). 1 This approach also achieved superior endoscopic remission (67% vs 44%), improved quality of life, and reduced hospitalizations and surgery. 1

Infliximab Dosing

• Induction: 5 mg/kg IV at weeks 0,2, and 6 3, 2
• Maintenance: 5 mg/kg IV every 8 weeks 3, 2
• Dose escalation: Consider 10 mg/kg for patients who initially respond but lose response 3, 2
• Combination therapy: Strongly recommended with thiopurine (azathioprine or 6-mercaptopurine) to improve efficacy and reduce immunogenicity 1, 2

Adalimumab Dosing

• Induction: 160 mg subcutaneous on Day 1 (single dose or split over two consecutive days), then 80 mg at Week 2 4, 2
• Maintenance: 40 mg subcutaneous every 2 weeks starting Week 4 4, 2
• Combination therapy: Consider with methotrexate, though evidence is less robust than for infliximab 2

Response Assessment

• Evaluate response to anti-TNF induction therapy between 8-12 weeks 2
• Patients who do not respond by Week 14 are unlikely to respond with continued dosing and should be switched to alternative therapy 3

Alternative First-Line Biologics

When anti-TNF therapy is contraindicated or patient preference favors different safety profile:

• Ustekinumab: Recommended for moderate-to-severe disease, particularly effective in anti-TNF naive patients 2
• Vedolizumab: Alternative option with potentially better safety profile but slower onset of action 2

Corticosteroids: Limited Role

Corticosteroids should NOT be used as monotherapy for maintenance and have significant limitations even for induction. 5, 6

When to Use Corticosteroids

• Prednisone 40-60 mg/day: Only for patients who have failed budesonide and require bridge therapy while initiating biologics 2
• Budesonide 9 mg/day: For mild-to-moderate disease limited to ileum/ascending colon as temporizing measure 7
• Evaluate response: Assess at 2-4 weeks 2

Critical Limitations

• Nearly 50% of patients become steroid-dependent or relapse within 1 year 5, 6
• Ineffective for maintaining remission or achieving mucosal healing 5
• Significant adverse effects: bone loss (even with short-term use), metabolic complications, increased intraocular pressure, and serious infections 5, 2
• Never use for maintenance therapy 2, 5

Immunomodulators: Not for Acute Flares

• Thiopurines (azathioprine, 6-mercaptopurine): NOT recommended as monotherapy for induction due to slow onset of action (8-12 weeks) 1, 2
• Role: Combination therapy with anti-TNF agents or maintenance after corticosteroid-induced remission 1, 2
• Methotrexate: Parenteral (subcutaneous/intramuscular) formulation may be used for induction and maintenance, but oral formulation is not recommended 2

Treatment Algorithm for Flares

New Diagnosis or First Flare

1. Initiate anti-TNF therapy immediately (infliximab or adalimumab) with combination immunomodulator 1, 2
2. Bridge with corticosteroids only if necessary while awaiting biologic effect 1
3. Assess response at 8-12 weeks 2

Flare on Existing Anti-TNF Therapy

1. Check therapeutic drug levels and antibodies 2
2. If subtherapeutic levels: Dose escalate (infliximab to 10 mg/kg or shorten interval; adalimumab to weekly dosing) 3, 4
3. If adequate levels or high antibodies: Switch to different anti-TNF or alternative mechanism (ustekinumab, vedolizumab) 2

Primary Non-Response to Anti-TNF

• Switch to ustekinumab or vedolizumab (different mechanism of action) 2
• Do NOT continue ineffective anti-TNF therapy beyond Week 14 3

Critical Pitfalls to Avoid

• Delaying biologic therapy: The 2024 ECCO guidelines explicitly removed requirements for patients to "fail conventional therapy" before biologics, recognizing that early aggressive treatment prevents long-term complications 1
• Using corticosteroids for maintenance: This leads to steroid dependency and does not prevent disease progression 5, 2
• Inadequate dose optimization: Subtherapeutic dosing leads to loss of response and antibody development 2
• Continuing ineffective therapy: Chronic untreated inflammation, even if asymptomatic, results in poor outcomes including strictures, fistulas, and need for surgery 1

Safety Monitoring

Before initiating anti-TNF therapy:

• Screen for tuberculosis (QuantiFERON or PPD) 3, 4
• Screen for hepatitis B 3, 4
• Ensure no active infections 3, 4
• Warning: Hepatosplenic T-cell lymphoma risk with combination thiopurine therapy, particularly in young males—weigh benefits versus risks 3, 2