What is the updated protocol for using risankizumab (interleukin-23 (IL-23) inhibitor) for the treatment of chronic plaque psoriasis?

Updated Protocol for Risankizumab in Chronic Plaque Psoriasis

Risankizumab is FDA-approved for moderate-to-severe chronic plaque psoriasis with a standard dosing regimen of 150 mg subcutaneously at weeks 0 and 4, then every 12 weeks thereafter, demonstrating superior efficacy to both ustekinumab and adalimumab with 73-75% of patients achieving PASI 90 at week 16. 1, 2

Dosing and Administration

Standard Protocol:

• Loading doses: 150 mg subcutaneous injection at week 0 and week 4 3, 1
• Maintenance dosing: 150 mg every 12 weeks thereafter 3, 1
• Can be self-administered after proper training 1, 4
• Each 150 mg dose requires four 37.5 mg prefilled syringes administered sequentially at the same injection session 1

Preparation Requirements:

• Remove from refrigerator and allow to reach room temperature for 45-90 minutes before injection 1
• Do not shake, warm artificially, or use if frozen 1
• Inspect for discoloration, cloudiness, flakes, or large particles (clear to yellow liquid with possible tiny white/clear particles is normal) 1

Efficacy Benchmarks

Expected Response Rates at Week 16:

• PASI 90: 73-75% of patients 2
• PASI 100: 36-45% of patients 3, 2
• sPGA 0/1 (clear or almost clear): 84-88% of patients 2

Long-term Efficacy (Week 304/6 years):

• PASI 90: 86% of patients 5
• PASI 100: 54% of patients 5
• Demonstrates durable maintenance without loss of efficacy over extended treatment 5

Response Assessment Timeline

Assess treatment response at 12 weeks of continuous therapy to determine definitive positive or negative response 3. This is the critical decision point for continuation versus modification of therapy.

For partial responders at 12 weeks:

• Consider adding topical corticosteroids 3
• Consider adding vitamin D analogues 3
• Consider adding methotrexate 3
• Consider adding ultraviolet B phototherapy 3
• While no published data supports combination therapy with IL-23 inhibitors, such combinations are not considered unsafe 3

Special Populations and Considerations

Biologic-Experienced Patients:

• Risankizumab remains effective in patients who failed other biologics, though response rates may be lower 6
• Real-world data shows patients previously treated with 2 or more biologics have significantly reduced likelihood of achieving PASI 75/90 at week 16 and PASI 90/100 at week 40 compared to first-line use 6
• Switching from adalimumab or ustekinumab to risankizumab can recapture response, with durable efficacy maintained through >2.5 years 4

Body Weight Considerations:

• Higher body mass index decreases likelihood of achieving PASI 90 at week 40 6
• Unlike ustekinumab, risankizumab dosing is not weight-based; all patients receive 150 mg regardless of weight 1, 2

Immunosuppressed Patients:

• Use caution in patients with pre-existing immunosuppression-related conditions 3
• Consider baseline pulmonary function testing in patients with respiratory comorbidities 7
• Ensure prophylactic vaccination against pneumococcal and influenza infections before initiating therapy 7

Safety Monitoring

Baseline Assessment:

• Screen for active infections, tuberculosis, and malignancy 3
• Establish baseline respiratory status if respiratory comorbidities present 7
• Complete indicated vaccinations (inactivated vaccines can be given during treatment; live vaccines require discontinuation) 3

Ongoing Monitoring:

• Treatment-emergent adverse events occur in approximately 46-50% of patients but are generally mild 8, 2
• Rates of adverse events remain stable over 6 years of continuous treatment 5
• More frequent follow-up during initial treatment period for patients with respiratory comorbidities 7

Treatment Interruption and Resumption

For Elective Surgery:

• Discontinue approximately 3-4 half-lives before surgery (risankizumab half-life allows for strategic timing) 3
• Resume 1-2 weeks after surgery if no postoperative complications 3
• Can continue through low-risk surgical procedures without interruption 3

Retreatment After Discontinuation:

• Consider repeating loading doses if patient is flaring and/or if more than 3-4 half-lives have passed since previous dose 3
• Note that retreatment may result in a small percentage of patients not recapturing their previous robust response 3

Comparative Positioning

Risankizumab demonstrates superior efficacy compared to:

• Ustekinumab: 75% vs 42% achieving PASI 90 at week 12 3
• Adalimumab: Higher PASI 90 rates with risankizumab in head-to-head trials 2
• Secukinumab and fumaric acid esters: Superior PASI 90 response rates in supportive trials 4

Long-term Malignancy Risk

The effect of risankizumab on solid tumor or lymphoreticular malignancy when used as monotherapy remains unknown 3. Large long-term follow-up studies are necessary to fully define cancer risk, though 6-year safety data shows no unexpected findings 5.