Generic Name

Skyrizi

Mechanism

Risankizumab binds with nanomolar affinity to the IL‑23p19 subunit,
• preventing IL‑23 from interacting with its IL‑23R on Th17 cells,
• halting the downstream production of IL‑17 and IL‑22 that drive keratinocyte proliferation,
• thereby interrupting the psoriatic inflammatory cascade.

The drug’s specificity limits off‑target effects and preserves TNF‑α and IL‑12 signaling, which contributes to its lower systemic immunosuppression.

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Pharmacokinetics

• Administration: Subcutaneous injection (SC).
• Absorption: 100 % bioavailability; peak serum concentration at ~7–9 days post‑dose.
• Distribution: Serum protein‑binding (~85 % to albumin).
• Metabolism: Largely catabolized via proteolytic pathways (IgG catabolism).
• Elimination: Renal and hepatic clearance is minimal; half‑life ~28 days (range 20‑40 days).
• Steady‑state: Achieved after 3–4 dosing intervals (every 12 weeks after the initial loading).
• Drug interactions: No clinically significant CYP450 interactions; no need for dose adjustment in hepatic or renal impairment (based on current data).

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Indications

• Moderate‑to‑severe plaque psoriasis (≥ > 10 % body surface area) in adults.
• Psoriatic arthritis (pending further evidence; investigational at time of writing).

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Contraindications

Contraindications
• Active, serious infections (e.g., tuberculosis, hepatitis B/C, HIV).
• Hypersensitivity to rasankizumab or any component of the formulation.

Warnings
• Infection risk: Includes upper respiratory tract infections; rare opportunistic infections (e.g., reactivation of latent TB).
• Increased mortality seen with certain biologics in patients with concomitant malignancy or systemic disease—use with caution.
• Pregnancy & lactation: Category X; avoid in pregnancy; insufficient data on lactation.

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Dosing

1. Initial dose: 150 mg SC (one pre‑filled syringe).
2. Maintenance: 150 mg SC at week 4, then every 12 weeks (q12w).
3. Administration site: Thigh, abdomen, or upper arm; rotate sites to reduce injection‑site reactions.

*Note*: Do not exceed 150 mg per dose. Use the 150 mg formulation for all indications to ensure consistent efficacy.

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Adverse Effects

Common (≥ 5 %)
• Upper respiratory tract infection (rhinitis, sinusitis)
• Injection‑site reaction (pain, erythema, induration)
• Headache, nasopharyngitis

Serious (≤ 1 %)
• Serious bacterial infections, including pneumonia and sepsis
• Opportunistic infections (latent TB reactivation)
• Rare infusion reactions (anaphylaxis)
• Potential malignancy (e.g., lymphoma) – not conclusively linked, but reported in biologic literature.

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Monitoring

• Baseline: CBC, comprehensive metabolic panel, hepatitis B/C serology, TB screening (IGRA or TST).
• During therapy:
• CBC and LFTs every 12 weeks.
• TB re‑screening annually if risk factors present.
• Monitor for signs of infection—prompt evaluation and treatment.
• Vaccinations: Ensure all routine immunizations (influenza, pneumococcal, COVID‑19) are up‑to‑date before initiating Skyrizi.

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Clinical Pearls

• TB Precaution: A negative IGRA/TST does not eliminate risk; maintain vigilance for TB symptoms during therapy.
• Injection‑Site Management: Use cool compresses immediately post‑injection; apply a light massage to disperse the drug and reduce erythema.
• Dose‑Interval Flexibility: If a dose is delayed by up to 4 weeks, a 150 mg rescue dose can restore immunologic suppression without compromising efficacy.
• Switching Biologics: Transitioning from a TNF‑α inhibitor to Skyrizi often results in improved skin clearance with minimal overlap toxicity.
• Patient Education: Emphasize consistent dosing schedule; irregular intervals can reduce therapeutic benefit and increase breakthrough flares.

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• *Prepared for medical students and health‑care professionals seeking a concise, reference‑ready overview of Skyrizi. For prescribing or detailed safety information, consult the latest prescribing information and professional guidelines.*