Is Skyrizi (risankizumab) the standard of care for ulcerative colitis?

Skyrizi (Risankizumab) is Not the Standard of Care for Ulcerative Colitis

Skyrizi (risankizumab) is not currently considered the standard of care for ulcerative colitis, though it has shown efficacy in clinical trials and is among the newer treatment options available. According to the most recent AGA guidelines (2024), multiple agents including TNF antagonists (infliximab, golimumab), vedolizumab, JAK inhibitors (tofacitinib, upadacitinib), and IL-12/23 or IL-23 antagonists (ustekinumab, risankizumab, guselkumab) are all recommended for moderate-to-severe ulcerative colitis 1.

Current Standard Treatment Approach for Ulcerative Colitis

The treatment approach for ulcerative colitis follows a stepwise algorithm based on disease severity:

1. First-line therapy:

   • 5-aminosalicylates (5-ASA) for mild-to-moderate disease
   • Oral corticosteroids for moderate disease not responding to 5-ASA

2. Maintenance therapy:

   • Aminosalicylates are the standard maintenance medical therapy for most patients 1
   • Thiopurines (azathioprine, mercaptopurine) for steroid-dependent disease

3. Advanced therapies for moderate-to-severe disease:

   • TNF antagonists (infliximab, adalimumab, golimumab)
   • Integrin antagonists (vedolizumab)
   • JAK inhibitors (tofacitinib, upadacitinib)
   • IL-12/23 antagonists (ustekinumab)
   • IL-23 antagonists (risankizumab, mirikizumab, guselkumab)

Evidence for Risankizumab in Ulcerative Colitis

Risankizumab has demonstrated efficacy in ulcerative colitis in recent clinical trials:

• In the INSPIRE induction trial, risankizumab 1200mg IV showed significantly higher clinical remission rates compared to placebo at week 12 (20.3% vs 6.2%) 2
• In the COMMAND maintenance trial, subcutaneous risankizumab (180mg and 360mg) demonstrated higher clinical remission rates at week 52 compared to placebo (40.2% and 37.6% vs 25.1%) 2
• Post-hoc analyses showed efficacy regardless of prior advanced therapy exposure, though with higher remission rates in biologic-naïve patients 3

Position of Risankizumab Among Treatment Options

The 2024 AGA guidelines recommend risankizumab as one of several effective options for moderate-to-severe ulcerative colitis, with a strong recommendation and moderate to high certainty of evidence 1. However, it is not positioned as the singular standard of care above other agents.

Important considerations:

• The AGA recommends TNF antagonists, vedolizumab, JAK inhibitors, IL-12/23 and IL-23 antagonists (including risankizumab) all with strong recommendations
• Treatment selection should consider:
  • Prior treatment failures
  • Comorbidities
  • Route of administration preferences
  • Insurance coverage/cost

Comparative Efficacy

While risankizumab has shown efficacy, other agents like mirikizumab (another IL-23 inhibitor) have also demonstrated significant efficacy in phase 3 trials, with clinical remission rates of 24.2% vs 13.3% for placebo at induction and 49.9% vs 25.1% at maintenance 4.

Clinical Algorithm for Treatment Selection

For moderate-to-severe ulcerative colitis:

1. First-line advanced therapy:

   • TNF antagonists (particularly infliximab) remain common first-line biologics
   • Consider combination with immunomodulators for TNF antagonists 1
   • JAK inhibitors generally recommended after TNF antagonist failure (FDA label restriction)

2. After TNF antagonist failure:

   • Switch to agent with different mechanism (vedolizumab, ustekinumab, JAK inhibitors, or IL-23 antagonists like risankizumab)
   • Consider patient-specific factors (comorbidities, administration route preference)

3. Special considerations for risankizumab:

   • May be particularly useful in patients who have failed other advanced therapies
   • Demonstrated efficacy in both biologic-naïve and biologic-experienced patients 3
   • Subcutaneous maintenance dosing may be preferred by some patients

Important Caveats

• Risankizumab is newer to the UC treatment landscape compared to some other biologics
• Long-term safety and efficacy data beyond 52 weeks is still being collected
• While effective, no single agent has emerged as clearly superior for all patients with moderate-to-severe UC
• Treatment costs and insurance coverage significantly impact real-world treatment selection

In conclusion, while risankizumab is an effective and recommended treatment option for moderate-to-severe ulcerative colitis, it is not currently positioned as the singular standard of care above other effective agents.