What is the treatment for Crohn's disease exacerbation?

Treatment of Crohn's Disease Exacerbation

First-line treatment for a Crohn's disease exacerbation should be conventional glucocorticosteroids (prednisolone, methylprednisolone, or intravenous hydrocortisone) for a first presentation or a single inflammatory exacerbation in a 12-month period. 1

First-Line Treatment Options

Conventional Glucocorticosteroids

• Recommended as first-line therapy due to direct evidence of benefit compared to other treatments and no treatment 1
• Should be used for a first presentation or a single inflammatory exacerbation in a 12-month period 1
• Health economic decision modeling has shown that starting with conventional glucocorticosteroid treatment is the most cost-effective approach for inflammatory exacerbation of Crohn's disease 1
• Even when accounting for risks of myocardial infarction and hip fracture associated with glucocorticosteroid therapy, this remains the most cost-effective strategy 1

Alternative First-Line Options for Specific Situations

Budesonide

• Consider for patients with distal ileal, ileocaecal, or right-sided colonic disease who decline, cannot tolerate, or have contraindications to conventional glucocorticosteroids 1
• Has fewer side effects than conventional glucocorticosteroids but is less effective 1
• Not recommended for severe presentations or exacerbations 1

Enteral Nutrition

• Consider as an alternative to conventional glucocorticosteroids for children and young people with concerns about growth or side effects 1

5-Aminosalicylates (5-ASA)

• Consider for patients who decline, cannot tolerate, or have contraindications to glucocorticosteroid treatment 1
• Less effective than conventional glucocorticosteroids or budesonide but may have fewer side effects than conventional glucocorticosteroids 1
• Not recommended for severe presentations or exacerbations 1

Second-Line/Add-on Therapy

Adding Immunomodulators

• Consider adding azathioprine or mercaptopurine to conventional glucocorticosteroids or budesonide if:
  • There are two or more inflammatory exacerbations in a 12-month period, or
  • The glucocorticosteroid dose cannot be tapered 1
• Assess thiopurine methyltransferase (TPMT) activity before offering azathioprine or mercaptopurine 1
• Do not offer azathioprine or mercaptopurine if TPMT activity is deficient 1
• Consider lower doses if TPMT activity is below normal but not deficient 1

Methotrexate

• Consider adding methotrexate to conventional glucocorticosteroids or budesonide if patients cannot tolerate azathioprine or mercaptopurine, or if TPMT activity is deficient, and:
  • There are two or more inflammatory exacerbations in a 12-month period, or
  • The glucocorticosteroid dose cannot be tapered 1

Biologic Therapy for Moderate-to-Severe Disease

TNF Inhibitors

• Recommended for patients with moderate-to-severe Crohn's disease who have not responded to conventional therapy 1
• Options include infliximab, adalimumab, and certolizumab pegol 1
• Consider combination therapy with a thiopurine when starting infliximab for better efficacy 1
• Infliximab is administered intravenously at 5 mg/kg at weeks 0,2, and 6 during induction and every 8 weeks thereafter 2

Ustekinumab

• Recommended for induction of remission in patients with moderate-to-severe Crohn's disease with inadequate response to conventional therapy and/or to anti-TNF therapy 1
• Administered intravenously for induction using a weight-based regimen of approximately 6 mg/kg 1

Upadacitinib

• Consider after failure of TNF-alpha inhibitors, providing an additional option with a novel mechanism of action 3
• Recommended for patients with primary non-response to TNF inhibitors, as an alternative to ustekinumab and vedolizumab 3

Important Monitoring Considerations

• Monitor for neutropenia in patients taking azathioprine or mercaptopurine even if they have normal TPMT activity 1
• Follow BNF/BNFC guidance on monitoring immunosuppressives 1
• Ensure documented local safety monitoring policies and procedures are in place 1
• Monitor for potential side effects of biologics including infections and malignancy 2

Treatment Approach Based on Disease Severity

Mild to Moderate Exacerbation

• Start with conventional glucocorticosteroids 1
• Consider budesonide for distal ileal, ileocaecal, or right-sided colonic disease 1
• Consider 5-ASA if glucocorticosteroids are contraindicated 1

Moderate to Severe Exacerbation

• Start with conventional glucocorticosteroids 1
• Consider early addition of immunomodulators if poor prognostic factors are present 1
• Consider biologic therapy if inadequate response to conventional therapy 1

Severe or Refractory Exacerbation

• Consider TNF inhibitors (infliximab, adalimumab, certolizumab pegol) 1
• Consider ustekinumab if inadequate response to anti-TNF therapy 1
• Consider upadacitinib after failure of TNF-alpha inhibitors 3

Special Considerations

Perianal Disease

• Treat any active proximal luminal disease with appropriate medications (budesonide, conventional corticosteroids, azathioprine, 6-mercaptopurine, methotrexate, infliximab) 1
• For simple perianal fistulas, consider antibiotics, fistulotomy, or immunosuppressants 1
• Infliximab is effective for both reduction in draining fistulas and maintenance of fistula closure 1, 2

Maintenance After Exacerbation

• Do not use conventional glucocorticosteroids or budesonide for maintenance of remission 1
• Consider azathioprine or mercaptopurine for maintenance, particularly in patients with adverse prognostic factors 1
• Consider methotrexate for maintenance only in specific situations (needed for induction, intolerance to azathioprine/mercaptopurine, or contraindications) 1