What is the recommended management approach for Crohn’s disease?

Management of Crohn's Disease

Early introduction of biologic therapy with or without immunomodulators is recommended for moderate to severe Crohn's disease rather than delaying their use until after failure of mesalamine and/or corticosteroids. 1

Disease Assessment and Treatment Strategy

• Disease severity should be determined based on a combination of symptoms, objective measures of inflammation, and factors that predict increased risk of complications 1
• Treatment approach should be tailored to the severity of disease and location, taking into account patient preferences 1
• Smoking cessation is critical for maintaining remission and should be strongly advised for all patients with Crohn's disease 1

Induction Therapy

Mild to Moderate Disease

• Ileal/Right Colonic Disease:

  • Oral budesonide 9 mg/day is suggested as first-line therapy 1
  • Evaluate response between 4-8 weeks to determine need for treatment modification 1

• Colonic Disease:

  • Sulfasalazine 4-6 g/day may be used for mild disease limited to the colon 1
  • Conventional corticosteroids (prednisolone 40-60 mg/day) for moderate disease that fails to respond to budesonide 1

Moderate to Severe Disease

• Conventional corticosteroids (prednisolone 40-60 mg/day, methylprednisolone, or IV hydrocortisone) are recommended for first presentation or single inflammatory exacerbation 1
• Biologic agents are recommended for patients who fail conventional induction therapies 1
  • Anti-TNF agents (infliximab, adalimumab)
  • Vedolizumab
  • Ustekinumab

Fistulating and Perianal Disease

• Metronidazole 400 mg three times daily and/or ciprofloxacin 500 mg twice daily as first-line treatment for simple perianal fistulae 1
• Azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day for simple perianal or enterocutaneous fistulae 1
• Infliximab (5 mg/kg at weeks 0,2, and 6) for perianal or enterocutaneous fistulae refractory to other treatments 1
• Surgical intervention (seton drainage, fistulectomy, advancement flaps) in combination with medical treatment for persistent or complex fistulae 1

Maintenance Therapy

• Corticosteroids (including budesonide) are not recommended for maintenance therapy 1
• Azathioprine (1.5-2.5 mg/kg/day) or mercaptopurine (0.75-1.5 mg/kg/day) are effective maintenance options for selected low-risk patients 1
• Methotrexate (15-25 mg weekly) is effective for patients whose active disease has responded to methotrexate 1
• Biologic agents should be continued in patients who responded to induction therapy with these agents 1:
  • Anti-TNF agents (infliximab 5-10 mg/kg every 8 weeks)
  • Vedolizumab
  • Ustekinumab

Therapies Not Recommended

• 5-Aminosalicylates (mesalamine) are not recommended for induction or maintenance therapy in moderate to severe disease 1, 2
• Antibiotics are not recommended for induction or maintenance of remission except in perianal disease 1
• Systemic corticosteroids should not be used for maintenance therapy 1
• Thiopurines should not be used for induction therapy 1

Special Considerations

Other Disease Locations

• Oral Crohn's disease: Manage with specialist in oral medicine; consider topical steroids, topical tacrolimus, intra-lesional steroid injections, enteral nutrition, or infliximab 1
• Gastroduodenal disease: Proton pump inhibitors often relieve symptoms 1
• Diffuse small bowel disease: Consider stricture dilatation or strictureplasty with nutritional support before and after surgery 1

Pediatric Considerations

• Exclusive enteral nutrition is suggested for induction therapy 1
• Anti-TNF agents are recommended for induction and maintenance therapy in severe disease or for patients who fail steroid and immunosuppressant therapies 1
• Adalimumab dosing for pediatric Crohn's disease (6 years and older) 3:
  • 17 kg to <40 kg: 80 mg on day 1,40 mg on day 15, then 20 mg every other week starting day 29
  • ≥40 kg: 160 mg on day 1,80 mg on day 15, then 40 mg every other week starting day 29

Monitoring and Follow-up

• Evaluate response to therapy within appropriate timeframes based on treatment:
  • Budesonide: 4-8 weeks 1
  • Corticosteroids: 2-4 weeks 1
  • Anti-TNF agents: 8-12 weeks 1
  • Vedolizumab: 10-14 weeks 1
  • Ustekinumab: 6-10 weeks 1
• Patients in clinical remission on immunomodulators should be assessed for mucosal healing within 1 year of treatment initiation 1

Treatment Paradigm Evolution

The treatment approach for Crohn's disease has evolved from a traditional step-up approach to an accelerated step-up or top-down approach for patients with moderate to severe disease or risk factors for complicated disease. Early aggressive therapy with biologics may modify disease course, promote mucosal healing, and reduce complications, hospitalizations, and surgeries 4, 5. However, this must be balanced against potential treatment-related risks including infections and malignancy 1, 5.