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

Treatment of Crohn's Disease Flare

For moderate to severe Crohn's disease flares, initiate systemic corticosteroids (prednisone 40-60 mg/day orally or methylprednisolone 40-60 mg/day IV if hospitalized) immediately, while simultaneously planning early introduction of biologic therapy with anti-TNF agents (infliximab or adalimumab) for maintenance to prevent steroid dependency 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 (C-reactive protein and fecal calprotectin) to distinguish true inflammatory flares from functional symptoms 2
• Exclude complications including intra-abdominal abscess, intestinal stricture with obstruction, or superimposed infections such as Clostridium difficile 2, 3
• Assess disease location and severity as this determines treatment selection—ileal/right colonic disease versus colonic disease versus extensive small bowel involvement 1, 2

Treatment Algorithm Based on Disease Severity and Location

Mild to Moderate Ileocecal Disease

For mild to moderate disease limited to the ileum and/or right colon, use oral budesonide 9 mg once daily for 8 weeks as first-line therapy. 1, 2

• Budesonide is as effective as prednisolone (51% vs 52.5% remission at 8 weeks) but with significantly fewer side effects 1
• Evaluate symptomatic response between 4-8 weeks to determine need for therapy modification 1
• Critical pitfall: Budesonide is inferior to systemic steroids when disease severity is high (CDAI >300) 1
• Taper budesonide over 1-2 weeks once remission is achieved 1

Mild Colonic Disease

For mild Crohn's disease limited to the colon, sulfasalazine 4-6 g/day can be used to induce remission, with response evaluated at 2-4 months 1

Important caveat: Oral 5-ASA products (mesalazine) are ineffective for both induction and maintenance of remission in Crohn's disease and should not be used 1, 2, 4

Moderate to Severe Disease (Any Location)

Initiate oral prednisone 40-60 mg/day immediately to induce remission. 1, 2

• This is a strong recommendation based on established efficacy—systemic corticosteroids are twice as effective as placebo for inducing remission 2
• Evaluate symptomatic response between 2-4 weeks; patients who fail to respond require escalation to biologic therapy 1, 3
• Taper prednisone by 5-10 mg weekly once remission is achieved, typically over 8-12 weeks 1, 3
• Rapid tapering (10 mg/week) should be considered where possible during the COVID-19 pandemic and similar high-risk situations, balanced against the risk of extending steroid exposure 1

Severe Disease Requiring Hospitalization

For patients requiring hospitalization, administer intravenous methylprednisolone 40-60 mg/day. 1, 3

• Assess response within 1 week—failure to respond mandates immediate escalation to biologic therapy 1, 3
• For high-risk patients (young age at diagnosis, extensive disease, perianal involvement, deep ulcerations, prior surgery), consider initiating anti-TNF therapy during hospitalization rather than waiting for corticosteroid response 3

Maintenance Therapy: The Critical Step

Corticosteroids must never be used for maintenance therapy—this is a strong recommendation to prevent steroid dependency and associated complications. 1, 2

When to Initiate Maintenance Therapy

Maintenance therapy should be initiated in the following scenarios:

• Patients who relapse more than once per year as steroids are withdrawn 1
• Steroid-dependent patients (unable to taper below 20 mg/day or relapse within 6 weeks of stopping steroids) 1, 3
• High-risk patients with moderate to severe disease at presentation 2, 3

First-Line Maintenance Options

Anti-TNF biologics (infliximab or adalimumab) are the preferred maintenance therapy for moderate to severe Crohn's disease. 2, 4, 3

Infliximab dosing 5:

• Induction: 5 mg/kg IV at weeks 0,2, and 6
• Maintenance: 5 mg/kg IV every 8 weeks
• For patients who lose response, consider increasing to 10 mg/kg 5
• Discontinue if no response by week 14 5

Adalimumab dosing 6:

• Adults: 160 mg on Day 1 (single dose or split over two consecutive days), 80 mg on Day 15, then 40 mg every other week starting Day 29
• Pediatric patients ≥40 kg: Same as adult dosing
• Pediatric patients 17-40 kg: 80 mg Day 1,40 mg Day 15, then 20 mg every other week

Combination therapy with anti-TNF 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. 2, 4, 3

• The landmark evidence shows combination therapy achieved sustained steroid- and surgery-free remission in 79% versus only 15% with traditional step-up care (p < 0.001) 4
• Critical warning: Hepatosplenic T-cell lymphoma, though rare, has been reported almost exclusively in patients receiving combination therapy with azathioprine or 6-mercaptopurine plus TNF-blockers, particularly in adolescent and young adult males with Crohn's disease 5, 6

Alternative Maintenance Options

For patients intolerant of or with contraindications to anti-TNF therapy:

• Ustekinumab is an alternative biologic, particularly effective in anti-TNF naive patients 2, 4
• Vedolizumab offers a potentially better safety profile but slower onset of action 4
• Parenteral methotrexate (15-25 mg subcutaneously weekly) for patients who achieved remission on methotrexate or who are intolerant of thiopurines 1, 2

For selected patients with lower-risk disease who achieved remission on corticosteroids:

• Thiopurine monotherapy (azathioprine or 6-mercaptopurine) can be considered 1, 2
• Monitor complete blood count within 4 weeks of starting therapy and every 6-12 weeks thereafter to detect neutropenia 1, 2

Monitoring and Response Assessment

• Evaluate response to anti-TNF therapy between 8-12 weeks—if no response by week 14, discontinue and switch to alternative biologic 2, 4
• Assess for steroid dependency during taper—patients requiring repeated courses or unable to taper below 10 mg/day require escalation to biologic or immunomodulator therapy 3
• Use therapeutic drug monitoring where possible to optimize anti-TNF dosing and identify patients who may benefit from combination immunosuppression 1

Critical Pitfalls to Avoid

Delaying biologic therapy in moderate to severe disease leads to long-term complications including strictures, fistulas, and need for surgery. 4

Using corticosteroids for maintenance causes steroid dependency (nearly 50% of patients become dependent or relapse within 1 year) and does not prevent disease progression. 7, 8, 9

Continuing ineffective therapy beyond the assessment window (4-8 weeks for budesonide, 2-4 weeks for prednisone, 8-14 weeks for biologics) results in unnecessary exposure to side effects without benefit. 1, 2, 5

Stopping or reducing medications without discussing with the IBD team risks flare leading to need for additional immunosuppression or hospitalization. 1

Corticosteroid side effects develop rapidly and can be severe, including increased risk of abdominal/pelvic abscesses, bone loss (even with short-term low-dose therapy), glucose intolerance, hypertension, glaucoma, and potentially lethal infections 2, 7, 9

Patients on high-dose steroids (≥20 mg prednisolone daily) should observe strict infection precautions as high-dose steroids are an established risk factor for respiratory tract and opportunistic infections. 1