What are the dosing schedule, required infection screening, contraindications, common and serious adverse effects, and alternative biologic options for Skyrizi (guselkumab) in adults with moderate‑to‑severe plaque psoriasis or active psoriatic arthritis?

Skyrizi (Guselkumab) for Moderate-to-Severe Plaque Psoriasis and Psoriatic Arthritis

Skyrizi (guselkumab) is dosed at 100 mg subcutaneously at weeks 0,4, and then every 8 weeks thereafter, with superior efficacy to adalimumab (70% vs 47% achieving PASI 90) and can be self-administered after proper training. 1, 2

Dosing Schedule

Standard Regimen:

• Loading doses: 100 mg subcutaneous injection at week 0 and week 4 2
• Maintenance: 100 mg every 8 weeks thereafter 2
• Self-administration: Patients can self-inject after proper training, or it can be administered by healthcare professionals 2
• No weight adjustment needed: Unlike ustekinumab, guselkumab dosing does not vary by body weight 2

Response Assessment:

• Assess definitive response after 12 weeks of continuous therapy (3 doses: weeks 0,4, and 12) 2
• For partial responders, consider adding topical corticosteroids, vitamin D analogues, methotrexate, or ultraviolet B light 1

Dosing Considerations:

• If a patient experiences a flare or if more than 45-72 days have passed since the previous dose (3-4 half-lives; guselkumab half-life is 15-18 days), repeat the week 0 and week 4 loading doses 2

Required Infection Screening

While the provided evidence does not specify exact screening protocols for guselkumab specifically, standard biologic screening protocols apply:

• Tuberculosis screening: PPD or interferon-gamma release assay before initiation 3
• Hepatitis B screening: HBsAg and anti-HBc testing 3
• Complete metabolic panel 3

Contraindications

The provided evidence does not explicitly list contraindications for guselkumab, but general biologic precautions apply:

• Active serious infections: Use caution in patients with pre-existing immunosuppression-related conditions 3
• Immunosuppressed patients: Exercise caution in patients with HIV or other immunosuppressive conditions 3

Adverse Effects

Common Adverse Events (Week 0-24):

• Infections: Most frequent adverse event, occurring in 16% of guselkumab-treated patients vs 20% of placebo patients 4
• Overall adverse event rate: 36% with guselkumab vs 33% with placebo in the first 24 weeks 4

Long-term Safety (Week 0-56):

• Adverse events occurred in 40% of guselkumab-treated patients, with no disproportional increase with longer exposure 4
• No deaths occurred in clinical trials 4
• Consistently favorable safety profile maintained over 3 years of continuous treatment 5

Serious Adverse Effects:

• Malignancy risk: The effect on solid tumor or lymphoreticular malignancy is unknown; large long-term follow-up studies are necessary 3
• Immunogenicity: Antibodies against guselkumab can develop, potentially leading to reduced drug levels and loss of efficacy 3

Efficacy Data

Plaque Psoriasis:

• PASI 90 achievement: 70.0-73.3% at week 16 in VOYAGE 1 and 2 trials 1
• Superior to adalimumab: 70.0% with guselkumab vs 46.8% with adalimumab vs 2.4% with placebo 1
• Biologic failures: Among adalimumab non-responders who switched to guselkumab, 66.1% achieved PASI 90 at week 48 1
• Long-term response: Sustained responses maintained for up to 5 years 1

Psoriatic Arthritis:

• ACR20 response: 58% with guselkumab vs 18% with placebo at week 24 (p<0.0001) 4
• FDA-approved for active psoriatic arthritis in 2020, making it the first selective IL-23 inhibitor for this indication 6

Special Sites:

• Scalp, nail, and palmoplantar psoriasis: Grade A recommendation for all three 1
• Same 100 mg dosing regimen applies to these difficult-to-treat areas 2

Alternative Biologic Options

Other IL-23 Inhibitors:

• Tildrakizumab: 100 mg at weeks 0,4, then every 12 weeks (longer interval than guselkumab) 3
• Risankizumab: Different dosing schedule than guselkumab 3, 2

IL-12/23 Inhibitor:

• Ustekinumab: 45 mg (≤100 kg) or 90 mg (>100 kg) at weeks 0,4, then every 12 weeks 3
• Grade A recommendation for moderate-to-severe plaque psoriasis 3
• Can be used with psoriatic arthritis 3

IL-17 Inhibitors:

• Ixekizumab: 160 mg at week 0, then 80 mg every 2 weeks until week 12, then 80 mg every 4 weeks 3
• Brodalumab: 210 mg at weeks 0,1,2, then every 2 weeks 3

TNF Inhibitors:

• Adalimumab, etanercept: Less effective than guselkumab for skin disease 3, 1
• For patients with both psoriatic arthritis and significant skin involvement, IL-23 inhibitors like guselkumab are preferred over TNF inhibitors 1

Clinical Positioning

Guselkumab receives Grade A recommendation from the American Academy of Dermatology and National Psoriasis Foundation for moderate-to-severe plaque psoriasis as monotherapy. 1, 7

Key Advantages:

• Superior efficacy compared to adalimumab and effective in biologic failures 1, 5
• Convenient dosing: every 8 weeks after loading (vs every 2-4 weeks for IL-17 inhibitors) 2
• Effective across multiple psoriasis subtypes including scalp, nail, and palmoplantar disease 1
• Well-tolerated with favorable long-term safety profile 5, 4

Common Pitfalls to Avoid:

• Do not confuse guselkumab dosing with other IL-23 inhibitors (tildrakizumab and risankizumab have different schedules) 2
• Do not weight-adjust the dose (unlike ustekinumab) 2
• Do not discontinue prematurely; allow the full 12-week assessment period (3 doses) before determining treatment failure 2