Is vedolizumab (Entyvio) indicated for patients with Crohn's disease who do not respond to infliximab (Remicade)?

Vedolizumab for Crohn's Disease After Infliximab Failure

Vedolizumab is strongly recommended for patients with Crohn's disease who have failed to respond to infliximab therapy, as it is effective for inducing and maintaining remission in this population. 1, 2

Efficacy in Anti-TNF Failure Patients

Vedolizumab has demonstrated significant efficacy in patients who have previously failed anti-TNF therapy:

• The European Crohn's and Colitis Organisation (ECCO) guidelines strongly recommend vedolizumab for moderate-to-severe Crohn's disease with inadequate response to conventional therapy and/or to anti-TNF therapy 1
• Clinical remission rates are significantly higher with vedolizumab compared to placebo (RR: 2.01; 95% CI: 1.50–2.71) 1
• Clinical response rates are also higher with vedolizumab compared to placebo (40.8% vs 25.7%; RR: 1.55; 95% CI: 1.14–2.11) 1, 2
• In patients who initially respond to vedolizumab induction, 27.7% of TNF-failure patients maintain remission at week 52 (versus 12.8% with placebo) 3

Dosing Recommendations

For patients with Crohn's disease who have failed infliximab:

• Standard dosing: 300 mg IV at weeks 0,2, and 6 for induction, then every 8 weeks for maintenance 2
• Patients who do not achieve response at Week 6 may benefit from an additional administration at Week 10 1
• Dose intensification to every 4 weeks may be considered for patients with inadequate response to standard dosing 2

Comparative Effectiveness

When comparing vedolizumab to other second-line biologics after anti-TNF failure:

• ECCO guidelines equally suggest either ustekinumab or vedolizumab for moderate-to-severe active luminal Crohn's disease in patients who have previously failed anti-TNF therapy 1
• Recent evidence suggests that at 52 weeks, vedolizumab may have higher clinical remission rates (55.5% vs 42.5%, p=0.01) and steroid-free remission rates (51.1% vs 40.6%, p=0.038) compared to ustekinumab in anti-TNF failure patients 4
• However, objective remission rates (based on endoscopy, MRI/CT, or ultrasound) were similar between vedolizumab and ustekinumab at 52 weeks 4

Safety Profile

Vedolizumab has a favorable safety profile:

• Rates of serious adverse events with vedolizumab are not significantly different from placebo (RR: 0.94; 95% CI: 0.61–1.45) 1, 2
• Most common adverse events include headache, nasopharyngitis, and infusion-related reactions (occurring in approximately 5% of patients) 2
• Unlike natalizumab (another integrin antagonist), vedolizumab is gut-selective, targeting only α4β7 integrin, making it unlikely to be associated with progressive multifocal leukoencephalopathy 5
• ECCO guidelines state that preoperative treatment with vedolizumab does not increase the risk of postoperative complications in patients with Crohn's disease having abdominal surgery 2

Monitoring Recommendations

For optimal management of patients on vedolizumab after infliximab failure:

• Evaluate clinical response between weeks 10-14 after initiation 2
• If dose escalation is needed, assess response within 8-12 weeks of the change 2
• Monitor for improvements in symptoms including stool frequency, abdominal pain, and nocturnal bowel movements 2
• Consider objective assessment of mucosal healing through endoscopy or imaging 2, 4

Important Considerations

• Efficacy appears similar regardless of the type of TNF-α antagonist failure (primary non-response, loss of response, or intolerance) 3
• Response rates are generally higher in TNF-naïve patients (48.9% remission at week 52) compared to TNF-failure patients (27.7% remission at week 52) 3
• The choice between vedolizumab and ustekinumab after anti-TNF failure should consider patient characteristics, preferences, costs, and local availability 1

In conclusion, vedolizumab is an effective and safe option for patients with Crohn's disease who have failed infliximab therapy, with strong supporting evidence from clinical guidelines and research studies.