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

Treatment of Crohn's Disease Flare

For moderate to severe Crohn's disease flares, initiate systemic corticosteroids (prednisolone 40 mg daily or equivalent) as first-line therapy, which is twice as effective as placebo for inducing remission, while simultaneously planning early introduction of biologic therapy with or without an immunomodulator to prevent future flares and disease progression. 1, 2

Initial Assessment Before Treatment

Before initiating therapy, confirm active inflammation and rule out complications that require different management:

• Measure biomarkers including fecal calprotectin and C-reactive protein to objectively confirm active inflammation rather than relying solely on symptoms 2
• Exclude complications such as intra-abdominal abscess, stricture with obstruction, or superimposed infection (including Clostridium difficile) that may mimic or complicate a flare 2
• Assess disease location and severity through endoscopy or cross-sectional imaging, as this determines optimal treatment selection 1, 2

Treatment Algorithm Based on Disease Severity and Location

Mild to Moderate Disease Limited to Ileum/Ascending Colon

Use budesonide 9 mg daily for 8 weeks, which is superior to placebo for inducing clinical response (RR 1.46) and remission (RR 1.93) with fewer systemic side effects than conventional corticosteroids 1, 2

• Budesonide has high topical anti-inflammatory activity with low systemic bioavailability, resulting in a better safety profile than prednisolone 1
• This recommendation applies specifically to disease confined to the ileum and/or ascending colon 1, 2

Moderate to Severe Disease (Any Location)

Initiate systemic corticosteroids immediately: prednisolone 40 mg daily or methylprednisolone equivalent, which induces remission in approximately 60% of patients compared to 30% with placebo 1, 2

• Taper corticosteroids gradually over 6-8 weeks once clinical response is achieved 2
• Never use corticosteroids for maintenance therapy due to significant adverse effects and lack of efficacy for preventing relapse 1, 2

What NOT to Use

Do not use mesalamine (5-ASA) products for Crohn's disease flares, as multiple high-quality trials and meta-analyses demonstrate they are ineffective for both induction and maintenance of remission in Crohn's disease 1, 2, 3

• Low-dose mesalamine (1-2 g/day) showed no superiority over placebo (RR 1.46,95% CI 0.89-2.40) 3
• High-dose mesalamine (4 g/day) produced only a clinically non-significant CDAI reduction of 19.8 points 3
• Sulfasalazine shows only modest benefit limited to colonic disease and is inferior to corticosteroids 1, 3

Concurrent Initiation of Maintenance Therapy

While treating the acute flare, simultaneously plan early introduction of biologic therapy (anti-TNF agents, vedolizumab, or ustekinumab) with or without an immunomodulator, rather than waiting for failure of corticosteroids 1, 2

Evidence for Early Biologic Introduction

The TOP-DOWN trial demonstrated that early combination therapy with infliximab plus immunosuppressant achieved corticosteroid-free remission in 61.5% of patients versus 42.2% with conventional step-up therapy (RR 0.67,95% CI 0.46-0.97) 1

• The REACT trial showed that early combination therapy reduced major adverse disease-related complications at 24 months (HR 0.73,95% CI 0.62-0.86) 1
• Early biologic therapy prevents disease progression, reduces hospitalizations, and decreases need for surgery 1, 2

Specific Biologic Options

First-line biologic: Infliximab 5 mg/kg IV at weeks 0,2, and 6, then every 8 weeks 4, 2

• Consider dose escalation to 10 mg/kg every 8 weeks for patients with inadequate response or loss of response 4
• Combination therapy with infliximab plus thiopurine is more effective than monotherapy for maintaining remission 2

Alternative biologics for anti-TNF failure or contraindications:

• Adalimumab 160 mg subcutaneous at week 0,80 mg at week 2, then 40 mg every 2 weeks 5
• Vedolizumab or ustekinumab 2

Maintenance Strategy After Flare Resolution

As corticosteroids are tapered, transition to maintenance therapy with one of the following:

Thiopurines (for steroid-dependent disease)

• Azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day 2
• Prevents repeated steroid exposure and associated complications 2
• Requires regular monitoring of blood counts regardless of TPMT status 2

Methotrexate (alternative to thiopurines)

• Particularly useful in steroid-dependent patients who cannot tolerate thiopurines 2

Biologic Monotherapy

• Continue infliximab 5-10 mg/kg every 8 weeks or adalimumab 40 mg every 2 weeks 4, 5
• Assess response to anti-TNF therapy between 8-12 weeks; if no response by week 14, discontinue and switch to alternative biologic 2

Critical Safety Considerations

Before Starting Biologics

Screen for latent tuberculosis, hepatitis B, and active infections before initiating anti-TNF therapy 4, 5

• Patients are at increased risk for serious infections including tuberculosis reactivation, invasive fungal infections, and opportunistic infections 4
• Treatment for latent tuberculosis must be initiated prior to biologic use 4

Corticosteroid Complications to Monitor

Monitor for abdominal/pelvic abscesses, Cushing syndrome, hypertension, diabetes, and osteoporosis in patients receiving systemic corticosteroids 2

Combination Therapy Risks

Hepatosplenic T-cell lymphoma, though rare, has been reported almost exclusively in young males receiving combination therapy with anti-TNF agents plus thiopurines 4

• This risk must be balanced against the superior efficacy of combination therapy 1, 2
• Consider therapeutic drug monitoring to potentially allow safe discontinuation of the immunomodulator while maintaining biologic efficacy 1

Common Pitfalls to Avoid

Do not delay appropriate therapy with ineffective agents: The step-up approach using mesalamine followed by corticosteroids before biologics leads to worse outcomes including higher rates of complications and surgery 1, 2

Do not use corticosteroids beyond the acute flare: Prolonged corticosteroid use increases infection risk without preventing relapse 1, 2

Do not assume clinical symptoms alone indicate disease activity: Always confirm with objective measures (biomarkers, endoscopy, imaging) as symptoms may be due to complications rather than active inflammation 2