What are the treatment options for immunotherapy in moderate to severe Crohn's disease?

Immunotherapy Options for Moderate to Severe Crohn's Disease

Biologic therapies, particularly anti-TNF agents, are the cornerstone of immunotherapy for moderate to severe Crohn's disease, with infliximab, adalimumab, and ustekinumab strongly recommended as first-line options over conventional therapies. 1

First-Line Biologic Options

Anti-TNF Agents

• Infliximab: Recommended at 5 mg/kg IV at weeks 0,2, and 6, followed by maintenance every 8 weeks 1, 2

  • Most effective when combined with thiopurines for biologic-naïve patients 1, 3
  • Achieves clinical remission in 39% of patients by week 30 (vs 21% with placebo) 3
  • Particularly effective for fistulizing disease (strong recommendation) 1

• Adalimumab: Effective alternative to infliximab 1

  • Typically administered subcutaneously (160 mg initially, then 80 mg every other week) 4
  • Combination with thiopurines may improve efficacy 1

• Certolizumab pegol: Less preferred than other anti-TNF options 1

  • Not recommended for fistulizing disease 1

Non-TNF Biologics

• Ustekinumab: Strongly recommended for both induction and maintenance 1

  • Effective in anti-TNF primary non-responders 1
  • Similar efficacy to infliximab and adalimumab 1

• Vedolizumab: Conditionally recommended 1, 5

  • Gut-selective α4β7 integrin inhibitor with favorable safety profile 6, 7
  • Particularly useful in patients with safety concerns about systemic immunosuppression 5, 6

Treatment Algorithm

1. For biologic-naïve patients:

   • First choice: Infliximab + thiopurine (conditional recommendation) 1, 3
   • Alternative first choices: Adalimumab + thiopurine, ustekinumab, or vedolizumab 1

2. For anti-TNF primary non-responders:

   • First choice: Ustekinumab (strong recommendation) 1
   • Second choice: Vedolizumab (conditional recommendation) 1

3. For secondary non-responders to infliximab:

   • First choices: Adalimumab or ustekinumab (strong recommendation) 1
   • Second choice: Vedolizumab (conditional recommendation) 1

4. For secondary non-responders to adalimumab:

   • Consider switching to infliximab (based on indirect evidence) 1

Immunomodulators

• Thiopurines (azathioprine, 6-mercaptopurine):

  • Not recommended as monotherapy for induction (conditional recommendation) 1
  • May be used for maintenance after corticosteroid-induced remission (conditional recommendation) 1
  • Most valuable when combined with biologics, particularly anti-TNFs 1, 3

• Methotrexate:

  • Subcutaneous/intramuscular route conditionally recommended for induction and maintenance 1
  • Oral route not recommended 1
  • May be used in combination with infliximab as an alternative to thiopurines 1

Special Considerations

Fistulizing Disease

• Infliximab is strongly recommended (highest level of evidence) 1
• Adalimumab, ustekinumab, and vedolizumab are conditionally recommended 1
• Biologic agents should be combined with antibiotics for perianal fistulas (strong recommendation) 1

Safety Monitoring

• Screen for tuberculosis before starting any biologic therapy 3, 2
• Monitor for serious infections, particularly with combination therapy 2
• Increased risk of lymphoma with combination of anti-TNF and thiopurines, particularly in young males 2
• Consider vedolizumab for patients with higher infection risk due to its gut-selective mechanism 6

Treatment Evaluation

• Assess response to therapy at 8-12 weeks 3
• Continue therapy if achieving remission or positive clinical response 3
• Consider dose escalation for infliximab (up to 10 mg/kg) in partial responders 2, 8
• Discontinue therapy if no response by week 14 2

Emerging Therapies

• Novel microbial-based immunotherapies are being investigated but require further research 9

The evidence strongly supports early introduction of biologic therapy rather than waiting for failure of conventional treatments like corticosteroids or mesalamine in moderate to severe Crohn's disease, as this approach leads to better long-term outcomes including reduced morbidity and improved quality of life 1, 3.