Is Skyrizi (Risankizumab) 600 mg IV at weeks 0, 4, and 8 medically necessary for a patient with longstanding Crohn's disease who has failed both Humira (Adalimumab) biosimilar and Entyvio (Vedolizumab), given their steroid-dependent disease pattern?

Medical Necessity Assessment for Skyrizi (Risankizumab) in Refractory Crohn's Disease

Yes, Skyrizi 600 mg IV at weeks 0,4, and 8 is medically necessary for this patient with longstanding, steroid-dependent Crohn's disease who has failed both Humira biosimilar (anti-TNF) and Entyvio (vedolizumab), and I recommend certification as medically necessary.

Rationale for Medical Necessity

Treatment Positioning After Multiple Biologic Failures

The patient meets clear criteria for IL-23 inhibitor therapy based on documented failure of two different biologic classes (anti-TNF and anti-integrin). 1 The Canadian Association of Gastroenterology strongly recommends ustekinumab (another IL-23 pathway inhibitor) for patients with moderate to severe Crohn's disease who fail to achieve complete remission with anti-TNF therapy (strong recommendation, moderate-quality evidence), and this same principle applies to risankizumab as an IL-23 inhibitor. 2

• The British Society of Gastroenterology specifically recommends risankizumab for patients with moderate-to-severe Crohn's disease who have had inadequate response to conventional therapies or previous biologic therapies, particularly TNF inhibitors (moderate certainty evidence). 1

• After vedolizumab failure in patients who have not responded well after switching from anti-TNF therapy, switching out of class to an IL-23 inhibitor represents an appropriate indication. 1

Evidence Supporting Risankizumab Efficacy

Risankizumab has demonstrated superior efficacy in the exact patient population described:

• In the phase 3 ADVANCE trial (biologic-experienced patients), risankizumab 600 mg achieved 45% CDAI clinical remission at week 12 versus 25% with placebo (adjusted difference 21%, p≤0.0001), and 40% endoscopic response versus 12% with placebo. 3

• In the MOTIVATE trial (biologic-refractory patients), risankizumab 600 mg achieved 42% CDAI clinical remission versus 20% with placebo, and 29% endoscopic response versus 11% with placebo. 3

• Real-world GETAID data in highly refractory patients (99% anti-TNF exposed, 93% vedolizumab exposed, 96% ustekinumab exposed) showed 46% steroid-free clinical remission at week 52 with risankizumab. 4

FDA-Approved Dosing Regimen

The FDA-approved induction regimen for Crohn's disease is precisely 600 mg IV at weeks 0,4, and 8, followed by subcutaneous maintenance. 5 The FDA label specifically requires obtaining liver enzymes and bilirubin levels prior to initiating treatment. 5

Addressing the Entyvio Timing Question

Current Entyvio Status Assessment

The documentation indicates the patient is likely still receiving Entyvio, but with documented inadequate response:

• The most recent note (page 22) documents "first maintenance injection of Entyvio at Q8W" with the patient stating "he continues to notice some improvements" but still having 2-3 bowel movements per day with variable consistency. [@user question@]

• The earlier note (pages 8-9) states the patient "does not think it's been working well" after being switched from Humira biosimilar. [@user question@]

• Page 20-21 documents the patient completed steroid taper approximately one week before an Entyvio infusion, then began having lower back ache and fatigue, which "usually occurs before a flare." [@user question@]

Recommendation to Proceed with Certification

Yes, proceed with certification despite ongoing Entyvio for the following reasons:

1. Documented inadequate response to vedolizumab: The patient's persistent symptoms (2-3 bowel movements daily, variable stool consistency, steroid-dependent pattern, pre-flare symptoms) constitute treatment failure even if Entyvio is ongoing. 2

2. Steroid-dependent disease pattern: The Canadian guidelines recommend against corticosteroids for maintenance of remission (strong recommendation, low-quality evidence), making the patient's steroid-dependent pattern a clear indication for escalation to alternative biologic therapy. 2

3. Evaluation timeline met: The Canadian guidelines suggest evaluating vedolizumab response between 10-14 weeks to determine need to modify therapy. 2 The patient has been on Entyvio since "over the summer" (multiple months), providing adequate time to assess response.

4. Sequential biologic failure: The patient has now failed two different mechanisms of action (anti-TNF and anti-integrin), making IL-23 inhibition the logical next step rather than continuing ineffective therapy. 1

Clinical Algorithm for This Decision

Follow this stepwise approach:

1. Confirm biologic failure documentation: ✓ Humira biosimilar failure documented; ✓ Entyvio inadequate response documented (persistent symptoms, steroid-dependent pattern, pre-flare symptoms)

2. Verify adequate trial duration: ✓ Entyvio used for several months (adequate for assessment per 10-14 week guideline timeframe) 2

3. Assess disease severity markers: ✓ Steroid-dependent pattern; ✓ Persistent bowel symptoms; ✓ Pre-flare symptoms documented

4. Confirm appropriate next-line therapy: ✓ IL-23 inhibitor appropriate after anti-TNF and vedolizumab failure 1

5. Verify FDA-approved regimen: ✓ 600 mg IV at weeks 0,4,8 is correct induction dosing 5

Safety Considerations and Pre-Treatment Requirements

Prior to initiating Skyrizi, ensure the following are completed:

• Obtain liver enzymes and bilirubin levels (FDA requirement for Crohn's disease indication). 5

• Evaluate for tuberculosis infection prior to treatment initiation. 5

• Complete age-appropriate vaccinations per current immunization guidelines. 5

• The safety profile in phase 3 trials showed similar adverse event rates to placebo, with no new safety signals in the biologic-refractory population. 3

Common Pitfalls to Avoid

Do not delay treatment based on:

• Ongoing Entyvio administration when inadequate response is documented—continuing ineffective therapy while disease remains active increases risk of complications and need for surgery. 4

• Waiting for "complete failure" or hospitalization—the steroid-dependent pattern and persistent symptoms already constitute treatment failure requiring escalation. 2

• Requiring additional anti-TNF trials—switching to a different anti-TNF after adalimumab failure is generally less effective than switching to a different mechanism of action. 1

Do ensure:

• Pre-treatment laboratory work is completed per FDA requirements (liver function tests, TB screening). 5

• Documentation clearly states inadequate response to vedolizumab (already present in this case with persistent symptoms and steroid-dependence). [@user question@]

• The patient understands this is induction therapy requiring three IV infusions followed by subcutaneous maintenance dosing. 5

Expected Outcomes

Based on the evidence, this patient can expect:

• Approximately 42-45% chance of achieving clinical remission by week 12. 3

• Approximately 29-40% chance of endoscopic response. 3

• In real-world highly refractory populations similar to this patient, 46% achieved steroid-free clinical remission at 52 weeks. 4

• Risankizumab persistence rate of 79% at week 52 in real-world cohorts. 4