What are the guidelines for monitoring and prescribing Skyrizi (risankizumab)?

Monitoring and Prescribing Skyrizi (Risankizumab)

Pre-Treatment Screening Requirements

Before initiating Skyrizi, screen for active infections, tuberculosis, and malignancy at baseline, and ensure prophylactic vaccination against pneumococcal and influenza infections is completed. 1

• Screen for active infections and tuberculosis using appropriate testing methods before starting therapy 1
• Assess for history of malignancy and current cancer risk factors 1
• Complete all indicated vaccinations prior to initiating immunosuppressive therapy 1
• Establish baseline respiratory status if the patient has respiratory comorbidities such as asthma or bronchiectasis 2
• Use caution in patients with pre-existing immunosuppression-related conditions, as these patients may have increased susceptibility to infections 3, 1, 2

Dosing Regimens by Indication

For Moderate-to-Severe Plaque Psoriasis

Administer 150 mg subcutaneously at weeks 0 and 4, then every 12 weeks thereafter for maintenance therapy. 1

• The standard induction consists of two loading doses at weeks 0 and 4 1
• Maintenance dosing of 150 mg every 12 weeks continues indefinitely for chronic plaque psoriasis 1
• Patients may use either the 90 mg/mL prefilled syringe (two syringes for 180 mg dose) or the 180 mg/1.2 mL prefilled cartridge with on-body injector 4

For Moderate-to-Severe Ulcerative Colitis

Administer intravenous induction followed by subcutaneous maintenance dosing. 4

• Induction phase: Administer intravenously, followed by subcutaneous maintenance 4
• Maintenance phase: Use 180 mg or 360 mg subcutaneously depending on clinical response 4
• The American Gastroenterological Association strongly recommends risankizumab for moderate-to-severe UC over no treatment (strong recommendation, moderate to high certainty of evidence) 5

Response Assessment Timeline

Assess treatment response at 12 weeks of continuous therapy to determine definitive positive or negative response. 1

• Week 12 assessment is the critical timepoint for determining treatment success 1
• Expected efficacy: 36-45% of psoriasis patients achieve PASI 100 (complete clearance) at week 16 1
• For partial responders at 12 weeks, consider adding topical corticosteroids, vitamin D analogues, methotrexate, or ultraviolet B phototherapy 1
• Week 16 benchmarks: 72-75% of patients achieve PASI 90 response 6
• Long-term efficacy: At week 304 (6 years), 86.0% achieved PASI 90 and 54.2% achieved PASI 100 with continuous treatment 7

Administration and Storage Guidelines

Storage Requirements

• Store refrigerated between 36°F to 46°F (2°C to 8°C) in the original carton to protect from light 4
• Allow to reach room temperature out of direct sunlight for 15-30 minutes (prefilled syringe) or 45-90 minutes (on-body injector) before use 4
• Do not shake, freeze, or expose to heat sources such as microwaves or hot water 4
• Do not use if expired, frozen (even if thawed), or if carton perforations are broken 4

Injection Technique

• Inject subcutaneously in the thigh, abdomen (at least 2 inches from navel), or upper outer arm (arm only by healthcare professional or caregiver) 4
• Do not inject into areas where skin is tender, bruised, erythematous, indurated, or affected by psoriasis lesions 4
• Rotate injection sites when administering multiple syringes for higher doses 4
• For on-body injector: Start injection within 5 minutes after inserting the prefilled cartridge; injection takes up to 15 seconds 4

Ongoing Monitoring Requirements

Infection Surveillance

Monitor vigilantly for respiratory symptoms and infections, particularly in patients with respiratory comorbidities. 2

• Schedule more frequent follow-up visits during the initial treatment period to monitor for respiratory symptoms 2
• Educate patients to promptly report any increase in respiratory symptoms, sputum production, or signs of infection 2
• Consider collaboration between specialties (e.g., rheumatology and pulmonology) for patients with complex comorbidities 2

Safety Monitoring

• Risankizumab may have a lower rate of infectious complications compared to TNF antagonists, which is beneficial for patients at higher risk 3, 5
• Most frequently reported adverse events include COVID-19 infection (8.6%) and nasopharyngitis (5.7%) 8
• Long-term safety data through 6 years shows low rates of treatment-emergent adverse events and adverse events leading to discontinuation 7

Perioperative Management

Discontinue risankizumab approximately 3-4 half-lives (approximately 12-16 weeks) before elective surgery. 1

• Resume risankizumab 1-2 weeks after surgery if no postoperative complications occur 1
• The terminal half-life is approximately 28 days with bioavailability of 89% following subcutaneous administration 1

Missed Dose Protocol

If a dose is missed, administer as soon as possible, then resume dosing at the regular scheduled time. 4

• Do not double doses to make up for missed administration 4
• Maintain the every-12-week schedule after administering the missed dose 4

Special Population Considerations

Pregnancy and Women of Childbearing Age

• Limited data exist on IL-23 inhibitors in pregnancy, but safety profile is expected to be similar to ustekinumab, which shows no significant increase in adverse pregnancy outcomes 3
• Avoid JAK inhibitors and S1P receptor modulators in women actively contemplating pregnancy; select risankizumab as an alternative when possible 3

Patients with Prior Biologic Failure

Risankizumab demonstrates superior efficacy in biologic-experienced patients, including those who failed IL-17 inhibitors. 8, 9

• For ulcerative colitis patients with prior biologic exposure, risankizumab is classified as intermediate efficacy by AGA guidelines 3
• Direct switching from IL-17 inhibitors (secukinumab or ixekizumab) to risankizumab without washout achieved sPGA 0/1 in 57.4% at week 16 and 62.3% at week 52 8
• Switching from ustekinumab or adalimumab showed durable and improved efficacy through >2.5 years of continuous exposure 10

Comparative Efficacy Data

Risankizumab demonstrates superior efficacy compared to ustekinumab, with 75% vs 42% achieving PASI 90 at week 12. 1

• Superior to adalimumab: 72-75% vs 47% achieved PASI 90 at week 16 6
• Superior to secukinumab: Demonstrated higher PASI 90 response rates in head-to-head trials 10
• Consistent efficacy regardless of baseline characteristics: Superior to ustekinumab across all patient demographics, disease severity, body weight, and prior biologic exposure 9