What is Skyrizi (Risankizumab)?

What is Skyrizi (Risankizumab)?

Skyrizi (risankizumab-rzaa) is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that selectively targets the p19 subunit of interleukin-23 (IL-23), inhibiting IL-23-dependent cell signaling and inflammatory pathways involved in psoriasis and psoriatic arthritis. 1

Mechanism of Action

• Risankizumab is an IL-23 antagonist that specifically binds to the p19 subunit of human IL-23 cytokine, inhibiting its interaction with the IL-23 receptor 1
• By targeting IL-23, risankizumab blocks a key regulatory cytokine implicated in psoriatic arthritis pathophysiology, including bone remodeling, enthesitis, synovitis, and psoriatic lesions 2
• IL-23 inhibition reduces the release of pro-inflammatory cytokines and chemokines involved in the inflammatory cascade 1

Formulations and Administration

• Skyrizi is available in several formulations:

  • 90 mg/mL prefilled syringe for subcutaneous use 1
  • 150 mg/mL prefilled syringe or prefilled pen for subcutaneous use 1
  • 180 mg/1.2 mL (150 mg/mL) prefilled cartridge with on-body injector 1
  • 360 mg/2.4 mL (150 mg/mL) prefilled cartridge with on-body injector 1
  • 600 mg/10 mL (60 mg/mL) solution in a vial for intravenous infusion 1

• Administration varies by indication:

  • For plaque psoriasis and psoriatic arthritis: subcutaneous injection 1
  • For Crohn's disease and ulcerative colitis: initial intravenous infusion followed by subcutaneous maintenance dosing 1

Approved Indications

• Moderate to severe plaque psoriasis in adults who may benefit from systemic therapy or phototherapy 1, 3
• Active psoriatic arthritis in adults 1, 2
• Moderate to severe Crohn's disease in adults 1, 4
• Moderate to severe ulcerative colitis in adults 1

Efficacy

Psoriasis

• In phase III trials (UltIMMa-1, UltIMMa-2, IMMvent, and IMMhance), risankizumab demonstrated superior efficacy compared to placebo, ustekinumab, and adalimumab 3, 5
• 72-75% of patients achieved PASI 90 (≥90% improvement in Psoriasis Area and Severity Index) with risankizumab compared to 2.0-4.9% with placebo, 42-48% with ustekinumab, and 47% with adalimumab 5
• Long-term data from the LIMMitless extension study showed sustained efficacy through 6 years of continuous treatment, with 86% of patients maintaining PASI 90 at week 304 6

Psoriatic Arthritis

• Risankizumab has demonstrated efficacy in decreasing the number of swollen and tender joints, clearing psoriatic plaques, and improving quality of life in patients with psoriatic arthritis 2
• The 2023 EULAR guidelines recognize risankizumab as one of the novel biological DMARDs targeting IL-23-p19 that has shown efficacy for the treatment of psoriatic arthritis 4

Safety Profile

• Risankizumab is generally well-tolerated in both short-term and long-term treatment 3, 6
• Most common adverse events include:
  • Upper respiratory tract infections 2
  • Mild localized infections 4
• Safety considerations:
  • Increased risk of infections due to immunosuppressive effects 1
  • Live vaccines should be avoided during treatment and immediately prior to or after treatment 1
  • Patients should be monitored for signs of infection and tuberculosis before and during treatment 1
  • Allergic reactions may occur, requiring immediate medical attention 1

Positioning in Treatment Algorithms

• For psoriatic arthritis:

  • The 2019 EULAR recommendations note that biologicals targeting IL-23-p19 (including risankizumab) appear encouraging, particularly for skin manifestations 4
  • IL-23 inhibitors like risankizumab have shown excellent efficacy in psoriasis 4
  • For patients with both psoriatic arthritis and significant skin involvement, IL-23 inhibitors or IL-17 inhibitors are recommended over TNF inhibitors 4, 7

• For inflammatory bowel disease:

  • Risankizumab is recommended for induction and maintenance therapy in moderate-to-severe Crohn's disease 4
  • The 2024 ECCO guidelines provide strong recommendations for risankizumab in Crohn's disease based on high-quality evidence 4

Special Considerations

• Caution is advised in patients with pre-existing immunosuppression-related conditions 7
• Patients with respiratory comorbidities may require more vigilant monitoring for infections 7
• Prophylactic vaccination against pneumococcal and influenza infections should be considered before initiating therapy 7
• Pregnancy: There is a pregnancy registry to monitor outcomes in women exposed to SKYRIZI during pregnancy 1

In summary, Skyrizi (risankizumab) represents an important targeted biologic therapy that selectively inhibits IL-23 through its p19 subunit, providing effective treatment for multiple inflammatory conditions with a favorable safety profile.