What are the guidelines for treating Crohn's disease?

Guidelines for Crohn's Disease Medical Management

Induction Therapy for Active Disease

Mild-to-Moderate Disease (Ileal/Right Colon)

For mild-to-moderate Crohn's disease limited to the ileum and/or ascending colon, use budesonide 9 mg daily for 8 weeks as first-line therapy. 1

• Budesonide demonstrates superior efficacy to placebo for inducing clinical response (RR: 1.46) and remission (RR: 1.93) while maintaining a favorable safety profile due to high first-pass hepatic metabolism and minimal systemic absorption 1
• Budesonide is more effective than mesalamine (Pentasa 4 g/day) for induction, with clinical response seen more frequently (RR: 1.22) 1
• The better safety profile compared to systemic corticosteroids makes budesonide the preferred corticosteroid option for this disease location 1, 2

Moderate-to-Severe Disease or Extensive Distribution

For moderate-to-severe Crohn's disease or disease beyond the ileum/ascending colon, use systemic corticosteroids (prednisolone 40-60 mg/day or methylprednisolone 48 mg/day) with weekly tapering over 8-12 weeks. 1, 2

• Systemic corticosteroids are twice as effective as placebo for inducing clinical remission (RR: 1.99) 1
• Clinical response occurs in 93.6% of patients versus 53.4% with placebo (RR: 1.75) 1
• Critical caveat: Adverse events occur 5-fold more frequently than placebo (31.8% vs 6.5%), including Cushing syndrome, infections (particularly abdominal/pelvic abscesses), hypertension, diabetes, osteoporosis, and growth failure in children 1, 3
• Evaluate response within 2-4 weeks; if inadequate, escalate to biologic therapy 2

Colonic Disease Only

For disease limited to the colon, sulfasalazine shows modest efficacy (RR: 1.38 for remission) with benefit confined to colonic involvement 1

What NOT to Use

Do not use 5-ASA/mesalamine for induction of remission in Crohn's disease. 1

• Meta-analysis of seven RCTs showed no significant effect for clinical remission (RR: 1.28; 95% CI: 0.97-1.69) 1
• High-dose mesalamine (3-4.5 g/day) is not superior to placebo for inducing remission or response 1
• Antibiotics (metronidazole, ciprofloxacin) have not consistently demonstrated efficacy for luminal Crohn's disease and should be reserved for septic complications 1, 2

Maintenance Therapy After Achieving Remission

Early Biologic Introduction Strategy

After achieving remission with corticosteroids, introduce anti-TNF biologics (infliximab or adalimumab) with or without immunomodulators for maintenance, particularly in moderate-to-severe disease or high-risk patients. 1, 2, 3

• Combination therapy with infliximab plus thiopurine is more effective than monotherapy for maintaining remission 2
• Infliximab dosing: 5 mg/kg IV at weeks 0,2, and 6, then every 8 weeks; may increase to 10 mg/kg if response is lost 4
• Assess response to anti-TNF therapy between 8-12 weeks; discontinue and switch to alternative if no response by week 14 2
• FDA indication: Infliximab is indicated for reducing signs/symptoms, inducing/maintaining remission, and reducing draining fistulas in moderate-to-severe Crohn's disease 4

Immunomodulator Options

Consider thiopurines (azathioprine, mercaptopurine) or methotrexate for maintenance therapy after corticosteroid-induced remission. 2, 3

• Thiopurines are strongly recommended for steroid-dependent disease 3
• Methotrexate should be administered subcutaneously at ≥15 mg weekly with folic acid supplementation 2
• Important limitation: Thiopurines as monotherapy are NOT recommended for induction of moderate-to-severe disease (RR: 1.23; 95% CI: 0.97-1.55 versus placebo) 1
• Critical warning: Hepatosplenic T-cell lymphoma (HSTCL), often fatal, has been reported in patients receiving TNF blockers with concomitant azathioprine/mercaptopurine, particularly in adolescent/young adult males with Crohn's disease 4

Alternative Biologic for Mild Disease

For select patients with mild-to-moderate Crohn's disease who require maintenance beyond budesonide, vedolizumab (gut-specific biologic) may be appropriate 5

• Vedolizumab is FDA-indicated for moderately-to-severely active Crohn's disease 6
• Dosing: 300 mg IV at weeks 0,2, and 6, then every 8 weeks; alternatively, can switch to 108 mg subcutaneous every 2 weeks after initial IV loading 6

Critical Management Principles

Monitoring and Treatment Targets

• Monitor disease activity with objective markers (endoscopy, CRP, fecal calprotectin) rather than symptoms alone 1
• Target endoscopic or histologic remission for better long-term outcomes 1
• Implement surveillance for therapy-related complications: vaccinations, osteoporosis screening, skin cancer monitoring 1

Corticosteroid Cautions

Never use corticosteroids for maintenance therapy. 3

• Most patients become steroid-refractory or steroid-dependent 7
• Budesonide has been ineffective as maintenance therapy despite efficacy for induction 7, 8
• Transition to immunomodulators or biologics while tapering steroids 2, 3

Special Populations

• Update immunizations before initiating biologics 6
• Screen for latent tuberculosis before starting anti-TNF therapy; treat if positive 4
• Infliximab doses >5 mg/kg are contraindicated in moderate-to-severe heart failure 4