Is Skyrizi (risankizumab) 600 mg IV at weeks 0, 4, and 8 medically necessary for a patient with longstanding Crohn’s disease of both small and large intestine without other complications, who has not responded to Entyvio (vedolizumab) and previously failed Humira (adalimumab) biosimilar?

Skyrizi (Risankizumab) for Crohn's Disease After Vedolizumab Failure

Yes, Skyrizi 600 mg IV at weeks 0,4, and 8 is medically necessary for this patient with longstanding Crohn's disease who has failed both Humira biosimilar and Entyvio (vedolizumab), particularly given the patient's steroid-dependent disease pattern. 1, 2

Rationale for Approval

Treatment Sequencing After Multiple Biologic Failures

• This patient has documented failure of two different biologic classes (anti-TNF with Humira biosimilar and anti-integrin with Entyvio), which strongly supports switching to an IL-23 inhibitor as the next therapeutic option 3

• Guidelines explicitly recommend IL-23 inhibitors (including risankizumab) for patients with moderate-to-severe Crohn's disease who have failed anti-TNF therapy, with strong recommendation and moderate-quality evidence 4

• The British Society of Gastroenterology specifically recommends risankizumab for Crohn's disease patients with inadequate response to conventional therapies or previous biologic therapies, particularly TNF inhibitors 4

Evidence Supporting Risankizumab in This Clinical Scenario

• Risankizumab demonstrated superior efficacy in biologic-experienced patients in the MOTIVATE trial, achieving CDAI clinical remission in 42% (600 mg dose) versus 20% with placebo at week 12 2

• Endoscopic response rates with risankizumab 600 mg were 29% versus 11% with placebo in biologic-experienced patients, representing a clinically meaningful difference 2

• Network meta-analysis data suggest risankizumab is associated with higher odds of inducing remission than vedolizumab in patients with previous biologic exposure (OR 2.10,95% CI 1.12-3.92) 5

FDA-Approved Dosing Regimen

• The FDA-approved induction regimen for Crohn's disease is precisely 600 mg IV at weeks 0,4, and 8, administered over at least one hour 1

• Following induction, maintenance dosing is 180 mg or 360 mg subcutaneously at week 12 and every 8 weeks thereafter, using the lowest effective dose to maintain response 1

Addressing the Steroid-Dependency Pattern

• The patient's report of feeling best on prednisone indicates steroid-dependent disease, which is a clear indication for escalation to more effective biologic therapy 3

• Guidelines recommend against using corticosteroids for maintenance of remission (strong recommendation), making the need for effective steroid-sparing biologic therapy urgent 3

• Vedolizumab failure in this context (patient not responding well after switching from anti-TNF) represents an appropriate indication to switch out of class to an IL-23 inhibitor 3

Safety Considerations

Pre-Treatment Requirements Met

• QuantiFERON Gold has been ordered (appropriate tuberculosis screening prior to biologic initiation, though results should be documented before first dose) 1

• No active serious infection documented (appropriate for biologic therapy initiation) 1

• No live vaccines noted (appropriate, as live vaccines should be avoided during IL-23 inhibitor treatment) 4

Liver Function Monitoring

• Liver enzymes and bilirubin levels must be obtained prior to initiating Skyrizi for Crohn's disease, as specified in the FDA label 1

• This should be documented before the first infusion is administered 1

Safety Profile

• Risankizumab demonstrated acceptable safety in both ADVANCE and MOTIVATE trials, with treatment-emergent adverse event rates similar to placebo 2

• Long-term safety data from the open-label extension study showed no new safety signals over a median of 33 months of treatment, with serious adverse event rate of 24.6 events/100 patient-years 6

• Serious infection rate was 4.2 events/100 patient-years, with no deaths, malignancies, or tuberculosis reported in the long-term extension study 6

Clinical Pitfalls to Avoid

• Do not delay treatment waiting for vedolizumab to "work better" – guidelines recommend evaluating vedolizumab response between 10-14 weeks, and this patient has already been on it since summer with inadequate response 3

• Ensure QuantiFERON Gold results are documented and negative before administering the first dose – this is a critical safety requirement 1

• Obtain baseline liver function tests before first infusion – this is an FDA requirement specific to Crohn's disease and ulcerative colitis indications 1

• Do not continue prednisone long-term – the goal is to achieve steroid-free remission with risankizumab, and corticosteroids should be tapered as the biologic takes effect 3

Alternative Considerations

• Ustekinumab would be another reasonable IL-23 pathway inhibitor option (targeting IL-12/23 p40 rather than IL-23 p19 specifically), with strong recommendation for patients who fail anti-TNF therapy 3

• However, risankizumab may offer advantages in biologic-experienced patients based on network meta-analysis data showing superior odds of remission compared to vedolizumab 5

• Switching to a different anti-TNF after adalimumab failure is generally less effective than switching to a different mechanism of action 3