What is the typical treatment approach for a Crohn's flare?

Treatment of Crohn's Disease Flare

For hospitalized patients with severe Crohn's disease flare, initiate intravenous methylprednisolone 40-60 mg/day immediately, and for moderate-to-severe outpatient flares, use oral prednisolone 40 mg daily, while 5-aminosalicylates should not be used as they are ineffective for inducing remission. 1, 2, 3

Initial Assessment and Exclusion of Complications

Before initiating medical therapy, rule out complications that require specific interventions rather than immunosuppression alone 1:

• Intra-abdominal abscess - requires drainage, not steroids
• Intestinal stricture with obstruction - may need endoscopic or surgical intervention
• Superimposed infection - particularly Clostridium difficile colitis 1

Confirm active inflammation using biomarkers (C-reactive protein, fecal calprotectin) to distinguish true inflammatory flares from functional symptoms, as treating non-inflammatory symptoms with immunosuppression exposes patients to unnecessary risk 1, 2

Assess disease location (ileal, colonic, ileocolonic), pattern (inflammatory, stricturing, fistulating), and severity, as these factors determine treatment selection 4, 2, 3

Treatment Algorithm Based on Disease Severity

Mild to Moderate Ileocecal Disease

Budesonide 9 mg daily for 8 weeks is the preferred first-line agent for disease limited to the terminal ileum and/or ascending colon 4, 2, 3:

• Superior safety profile compared to systemic corticosteroids with fewer systemic side effects 3
• Marginally less effective than prednisolone but better tolerated 4
• Do not use budesonide for severe presentations 4

Alternative for patients who decline or cannot tolerate budesonide: high-dose mesalamine 4 g/daily may be considered, though it is significantly less effective than corticosteroids 4

Moderate to Severe Disease (Any Location)

Systemic corticosteroids are first-line therapy 4, 2, 3:

• Outpatient: Prednisolone 40 mg daily orally 4, 2
• Hospitalized: Methylprednisolone 40-60 mg/day or hydrocortisone 400 mg/day intravenously 4, 1
• Taper gradually over 8-12 weeks; more rapid reduction increases early relapse risk 4, 2

Evaluate response within 1-2 weeks - patients failing to respond require escalation to biologic therapy 1, 2

High-Risk Patients Requiring Early Biologic Therapy

For patients with poor prognostic factors, consider initiating anti-TNF therapy during the flare rather than waiting for corticosteroid response 4, 1:

High-risk features include:

• Young age at diagnosis
• Extensive disease
• Perianal involvement
• Deep ulcerations on endoscopy
• Prior intestinal surgery 1

Infliximab is preferred in the hospital setting due to intravenous administration and rapid onset, dosed at 5 mg/kg at weeks 0,2, and 6 1, 5

What NOT to Use for Crohn's Flares

5-aminosalicylates (mesalamine, sulfasalazine) are NOT recommended for inducing remission in Crohn's disease 4, 2, 3:

• Multiple high-quality trials demonstrate they are ineffective compared to placebo for moderate-to-severe disease 6
• The 2021 AGA guidelines explicitly state 5-ASA products are ineffective for both induction and maintenance 2
• This represents a critical pitfall, as these agents are still sometimes prescribed despite clear evidence of inefficacy 4, 2

Azathioprine, mercaptopurine, and methotrexate should NOT be used as monotherapy to induce remission - they are too slow-acting for acute flares 4

Maintenance Therapy After Achieving Remission

Corticosteroids must NEVER be used for maintenance therapy - they are ineffective and cause significant harm with long-term use 4, 2

Initiate maintenance therapy before discharge or while tapering steroids to prevent relapse 1, 2:

First-Line Maintenance Options

Anti-TNF biologics with or without immunomodulator combination 4, 1, 2:

• Combination therapy with infliximab plus thiopurine (azathioprine 2-2.5 mg/kg/day or 6-mercaptopurine 1-1.5 mg/kg/day) is more effective than monotherapy for maintaining remission 1, 3
• Adalimumab 40 mg subcutaneously every other week is an alternative 5
• Assess response between 8-12 weeks; if no response by week 14, discontinue and switch to alternative biologic 1, 2

Alternative Maintenance Options

Thiopurines (azathioprine or mercaptopurine) for steroid-dependent patients 4, 2:

• Check TPMT activity before initiating - do not use if deficient 4
• Consider lower doses if TPMT activity is below normal but not deficient 4
• Monitor blood counts regularly even with normal TPMT 2

Methotrexate 15-25 mg subcutaneously weekly with folic acid for patients intolerant to thiopurines or with TPMT deficiency 4, 1, 2

Monitoring and Steroid-Dependent Disease

Assess for steroid dependency - defined as inability to taper below 10 mg/day prednisone or requiring repeated courses within 12 months 1, 2:

• These patients require escalation to biologic or immunomodulator therapy 4, 2
• Adding azathioprine, mercaptopurine, or methotrexate to corticosteroids is appropriate when there are two or more inflammatory exacerbations in 12 months or inability to taper steroids 4

Important Safety Considerations

Monitor hospitalized patients with severe flares closely 4:

• Vital signs four times daily
• Daily stool chart documenting frequency, character, and blood
• CBC, ESR/CRP, electrolytes, albumin, liver function every 24-48 hours
• Daily abdominal radiography if colonic dilatation (transverse colon >5.5 cm) present 4

Subcutaneous heparin prophylaxis to reduce thromboembolism risk in hospitalized patients 4

Nutritional support (enteral or parenteral) if malnourished 4

Corticosteroid adverse effects require monitoring: increased infection risk (particularly abdominal/pelvic abscesses), Cushing syndrome, hypertension, diabetes, and osteoporosis 2