What is the best choice between Vedolizumab (Intyvio) and IL-23 inhibitors for treating moderate to severe Inflammatory Bowel Disease (IBD)?

Vedolizumab vs IL-23 Inhibitors for IBD: Comparative Efficacy and Safety

For moderate-to-severe inflammatory bowel disease (IBD), vedolizumab (Entyvio) is recommended as the preferred first-line biologic therapy over IL-23 inhibitors due to its established long-term safety profile, gut-selective mechanism of action, and strong evidence supporting its efficacy in both ulcerative colitis and Crohn's disease.

Efficacy Comparison

Vedolizumab (Entyvio)

• Strong recommendation for both induction and maintenance therapy in moderate-to-severe Crohn's disease with moderate-quality evidence 1
• Recommended for induction and maintenance of remission in UC with strong evidence 1
• Long-term data shows impressive remission rates: 83% of responders remained in remission after 2 years and 89% after 3 years 1
• Real-world effectiveness demonstrated in observational studies with steroid-free remission rates of 28.6-54% at one year 1
• Particularly effective in patients with disease duration ≤2 years in Crohn's disease 1

IL-23 Inhibitors (Risankizumab, Mirikizumab, Guselkumab)

• Strong recommendation for risankizumab and guselkumab in moderate-to-severe UC 1
• Conditional recommendation for mirikizumab in moderate-to-severe UC 1
• Clinical remission rates with risankizumab in UC: 18.5% vs 6.2% for placebo 1
• Clinical remission rates with mirikizumab in UC: 24.1% vs 11.8% for placebo 1
• Risankizumab showed efficacy in Crohn's disease with clinical remission rates of 51.8% vs 39.6% for placebo at week 52 1

Safety Profile Comparison

Vedolizumab

• Excellent safety profile with no unexpected long-term safety signals identified 2
• Gut-selective mechanism minimizes systemic immunosuppression 3
• Lower risk of serious infections compared to TNF antagonists (32% reduction in UC patients) 1
• Safe in special populations including pregnancy, elderly patients, and those with prior history of cancer 2
• Well-tolerated with high continuation rates beyond induction dosing 4

IL-23 Inhibitors

• Generally well-tolerated but with less long-term safety data compared to vedolizumab 1
• Ustekinumab (IL-12/23 inhibitor) showed 51% lower risk of serious infections compared to TNF antagonists in Crohn's disease 1
• Safety profile appears favorable but with shorter follow-up data compared to vedolizumab 1

Clinical Decision Algorithm

1. First-line biologic choice:

   • For patients with moderate-to-severe IBD (both UC and CD): Vedolizumab is preferred due to its established long-term safety profile and gut-selective mechanism 1, 2
   • For patients with high risk of infections or malignancy (elderly, immunocompromised): Vedolizumab is strongly preferred due to gut-selective immunosuppression 1

2. Consider IL-23 inhibitors when:

   • Patient has failed vedolizumab therapy 1
   • Patient has extraintestinal manifestations that may benefit from systemic immunomodulation 1
   • Specific comorbidities where IL-23 pathway inhibition may provide additional benefits 1

3. Dosing considerations:

   • Vedolizumab: 300mg IV at weeks 0,2, and 6 for induction, then every 8 weeks for maintenance 5
   • Consider dose escalation to every 4 weeks in partial responders - approximately 50% of patients achieve/recapture response with this strategy 6
   • IL-23 inhibitors: Follow specific dosing for each agent (risankizumab, mirikizumab, guselkumab) according to approved regimens 1

Special Considerations

• Prior anti-TNF failure: Vedolizumab remains effective even in anti-TNF failure patients, though response rates are somewhat lower compared to anti-TNF naïve patients 1
• Disease duration: Vedolizumab shows higher response rates in Crohn's disease of ≤2 years duration 1
• Combination therapy: Due to its safety profile, vedolizumab is an excellent candidate for combination therapy with other biologics or small molecules in refractory cases 2
• Subcutaneous formulation: Subcutaneous vedolizumab is now available as maintenance therapy with comparable efficacy to IV formulation, offering greater convenience 1

Conclusion on Best Choice

Vedolizumab represents the preferred option for moderate-to-severe IBD due to its established long-term safety profile, gut-selective mechanism minimizing systemic immunosuppression, and proven efficacy in both induction and maintenance of remission. While IL-23 inhibitors show promising results, the extensive long-term safety data and real-world experience with vedolizumab make it the superior choice for most patients with IBD, particularly those concerned about systemic immunosuppression or at higher risk for infections or malignancy.