Is anti-TNF (Tumor Necrosis Factor) therapy more effective than IL-23 (Interleukin 23) therapy for treating stricturing Crohn's disease?

Anti-TNF vs IL-23 Therapy for Stricturing Crohn's Disease

For patients with stricturing Crohn's disease, anti-TNF therapy is recommended as first-line biologic therapy over IL-23 inhibitors due to more robust evidence supporting its efficacy in this specific disease phenotype and stronger recommendations in current guidelines. 1

Evidence-Based Treatment Algorithm

First-Line Biologic Therapy Selection:

• Anti-TNF agents (infliximab or adalimumab) are strongly recommended as first-line biologic therapy for moderate to severe Crohn's disease, especially with risk factors of poor prognosis like stricturing disease 1
• The Canadian Association of Gastroenterology provides a strong recommendation with moderate-quality evidence for anti-TNF as first-line therapy 1

Optimizing Anti-TNF Therapy:

1. Combination therapy approach:

   • Combine anti-TNF with a thiopurine (preferred) or methotrexate to improve efficacy and pharmacokinetic parameters 1
   • This combination is particularly important for infliximab to reduce immunogenicity 1

2. Dosing and monitoring:

   • Evaluate response to anti-TNF induction at 8-12 weeks 1
   • For suboptimal response, consider dose intensification 1
   • Use therapeutic drug monitoring to guide dose optimization if response is lost 1

3. Maintenance strategy:

   • Continue anti-TNF therapy in responders to maintain complete remission (strong recommendation, high-quality evidence) 1

When to Consider IL-23 Inhibition (Ustekinumab):

• Consider as second-line therapy after anti-TNF failure 1
• Ustekinumab is recommended for patients who fail to achieve complete remission with anti-TNF therapy (strong recommendation, moderate-quality evidence) 1
• Evaluate response between 6-10 weeks 1

Comparative Efficacy Considerations

Anti-TNF therapy has several advantages for stricturing Crohn's disease:

1. Longer clinical experience and evidence base:

   • Anti-TNF agents have more extensive long-term data in Crohn's disease, particularly for complicated disease phenotypes like stricturing disease 1
   • Strong recommendations in guidelines specifically for moderate-to-severe disease with poor prognostic factors 1

2. Combination therapy benefits:

   • The SONIC study demonstrated that combination therapy with infliximab and azathioprine is superior to either agent alone 1
   • This approach is particularly beneficial for patients with aggressive disease features

3. Mucosal healing potential:

   • Anti-TNF agents have demonstrated ability to achieve mucosal healing, which may prevent stricture progression 1

Important Caveats and Considerations

• Immunogenicity concerns: Anti-TNF therapy, particularly infliximab, has higher immunogenicity rates than IL-23 inhibitors, which can be mitigated with combination therapy 1

• Safety profile differences:

  • Anti-TNF agents carry risks of opportunistic infections, particularly when combined with immunosuppressants 2
  • Consider individual patient risk factors (age, comorbidities) when selecting therapy

• Pediatric considerations:

  • In pediatric Crohn's disease, anti-TNF therapy is particularly important for growth-related outcomes in stricturing disease 1
  • Early aggressive therapy with anti-TNF is recommended for high-risk pediatric patients 1

• Treatment failure management:

  • If anti-TNF therapy fails, vedolizumab or ustekinumab are recommended as next options 1
  • Avoid switching between different anti-TNF agents if the first one fails, as this has lower success rates 1

While IL-23 inhibitors like ustekinumab show promise in Crohn's disease treatment, the current evidence and guidelines more strongly support anti-TNF therapy as the preferred first-line biologic option for patients with stricturing Crohn's disease, with IL-23 inhibitors positioned as effective second-line options after anti-TNF failure.