Introduction
Skyrizi (risankizumab-rzaa) is a humanized immunoglobulin G1 (IgG1) monoclonal antibody biologic medication developed by AbbVie. It represents a significant advancement in the treatment of moderate to severe plaque psoriasis and psoriatic arthritis. Approved by the FDA in 2019, Skyrizi specifically targets interleukin-23 (IL-23), a key cytokine involved in the inflammatory processes of these autoimmune conditions.
Mechanism of Action
Skyrizi exerts its therapeutic effect through highly selective inhibition of interleukin-23 (IL-23). The drug specifically binds to the p19 subunit of IL-23, preventing interaction with the IL-23 receptor complex. This targeted action disrupts the release of proinflammatory cytokines and chemokines, including IL-17, IL-22, and tumor necrosis factor-alpha (TNF-α). By inhibiting the IL-23/Th17 inflammatory pathway, Skyrizi reduces the epidermal hyperplasia, neutrophil infiltration, and abnormal keratinocyte differentiation characteristic of psoriatic lesions.
Indications
Skyrizi is FDA-approved for:
- Treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy
- Active psoriatic arthritis in adults
- Moderate to severe Crohn's disease in adults
Dosage and Administration
Standard Dosing:- Plaque Psoriasis: 150 mg (two 75 mg injections) administered subcutaneously at Week 0, Week 4, and every 12 weeks thereafter
- Psoriatic Arthritis: 150 mg administered subcutaneously at Week 0, Week 4, and every 12 weeks thereafter
- Crohn's Disease: 600 mg administered by intravenous infusion over at least 1 hour at Week 0, Week 4, and Week 8; followed by 360 mg subcutaneously at Week 12 and every 8 weeks thereafter
- Subcutaneous injections should be administered in the abdomen, thighs, or upper arms
- Rotate injection sites with each administration
- Allow prefilled syringe or pen to reach room temperature (15-30 minutes) before injection
- Renal Impairment: No dosage adjustment required
- Hepatic Impairment: No dosage adjustment required
- Elderly: No dosage adjustment required
- Pediatric: Safety and effectiveness not established
Pharmacokinetics
Absorption: Following subcutaneous administration, peak serum concentrations are achieved in approximately 3-14 days. Bioavailability is approximately 89%. Distribution: Steady-state volume of distribution is approximately 10.1 L. Risankizumab is expected to be distributed in the blood and extracellular fluid. Metabolism: Skyrizi is metabolized via proteolytic enzymes into small peptides and amino acids, similar to endogenous IgG antibodies. No cytochrome P450 enzyme involvement. Elimination: Terminal half-life is approximately 28 days. Clearance occurs through linear and nonlinear pathways, including target-mediated drug disposition.Contraindications
- History of serious hypersensitivity reaction to risankizumab-rzaa or any of its excipients
- Active tuberculosis or other serious infections
- Patients with known immunodeficiency syndromes
Warnings and Precautions
Infections: Skyrizi may increase the risk of infections. Serious infections have been reported. Patients should be evaluated for tuberculosis infection before initiating treatment. Hypersensitivity Reactions: Angioedema and urticaria have been reported. If a serious hypersensitivity reaction occurs, discontinue Skyrizi immediately and initiate appropriate therapy. Hepatotoxicity: Liver enzyme elevations have been observed. Consider monitoring liver enzymes at baseline and during treatment. Immunizations: Avoid live vaccines during treatment. Patients should receive all recommended vaccinations before initiating therapy. Theoretical Risk of Malignancy: Due to its mechanism of action, Skyrizi may increase the risk of malignancy. However, clinical trials did not demonstrate increased malignancy risk compared to placebo.Drug Interactions
- Live Vaccines: Avoid concurrent administration
- CYP450 Substrates: Skyrizi may affect the formation of CYP450 enzymes by altering cytokine levels
- Other Biologics: Increased risk of immunosuppression when used with other biologic immunosuppressants
Formal drug interaction studies have not been conducted due to the metabolic pathway of Skyrizi.
Adverse Effects
Common Adverse Reactions (≥1%):- Upper respiratory infections
- Headache
- Fatigue
- Injection site reactions
- Tinea infections
- Serious infections
- Hypersensitivity reactions
- Hepatic transaminase elevations
- Anaphylaxis
- Angioedema
- Urticaria
Monitoring Parameters
Baseline Assessment:- Complete blood count with differential
- Liver function tests
- Tuberculosis screening
- Hepatitis B and C screening
- Pregnancy test if applicable
- Monitor for signs and symptoms of infection
- Regular skin examinations for psoriasis improvement
- Liver function tests as clinically indicated
- Assessment of psoriatic arthritis symptoms and joint function
- Patient-reported outcomes and quality of life measures
- Annual tuberculosis screening in high-risk populations
- Regular assessment of treatment response and safety
- Monitoring for potential immunogenicity
Patient Education
Administration:- Proper injection technique and site rotation
- Storage requirements (refrigerate at 2°C to 8°C)
- Do not freeze or shake the medication
- Recognize signs of infection (fever, chills, cough)
- Report any allergic reactions immediately
- Inform healthcare providers about Skyrizi use before surgeries or dental procedures
- Importance of adherence to prescribed dosing schedule
- Avoid live vaccines during treatment
- Discuss family planning with healthcare provider
- Report new or worsening symptoms promptly
- Keep all scheduled medical appointments
- Report any side effects to healthcare provider
- Do not discontinue medication without medical guidance
References
1. FDA Prescribing Information: Skyrizi (risankizumab-rzaa). Updated 2023. 2. Gordon KB, et al. Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis: Results from the phase 3 IMMhance trial. British Journal of Dermatology. 2019;180(1):54-62. 3. Reich K, et al. Efficacy and safety of risankizumab compared with adalimumab in patients with moderate-to-severe psoriasis: Results from the phase 3 IMMvent trial. British Journal of Dermatology. 2019;180(3):504-513. 4. Papp KA, et al. Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis. New England Journal of Medicine. 2017;376(16):1551-1560. 5. Kristensen LE, et al. Efficacy and Safety of Risankizumab for Active Psoriatic Arthritis: 24-Week Results From the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Annals of the Rheumatic Diseases. 2022;81(2):225-231. 6. Ferrante M, et al. Efficacy and Safety of Risankizumab for Moderate-to-Severe Crohn's Disease: Results From the ADVANCE and MOTIVATE Trials. Gastroenterology. 2022;162(3):S1-S2.
This monograph is intended for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for medical advice.