Guselkumab

• Plaque Psoriasis
• Psoriatic Arthritis
• Moderate to Severe Psoriasis
• IL-23 Inhibitor Therapy

Guselkumab is a fully human monoclonal antibody that selectively blocks interleukin-23 (IL-23), used for the treatment of moderate to severe plaque psoriasis and active psoriatic arthritis. This biologic provides targeted inhibition of a key cytokine in the pathogenesis of psoriatic disease.

Mechanism of Action

Guselkumab is a human IgG1 lambda monoclonal antibody that selectively binds to the p19 subunit of interleukin-23 (IL-23), blocking its interaction with the IL-23 receptor. IL-23 is a cytokine that plays a central role in the pathogenesis of psoriasis and psoriatic arthritis. It promotes the differentiation and survival of Th17 cells, which produce pro-inflammatory cytokines including IL-17A, IL-17F, and IL-22. These cytokines drive keratinocyte proliferation and inflammation in psoriatic plaques. By selectively blocking IL-23 (without affecting IL-12, which shares the p40 subunit), guselkumab interrupts this inflammatory cascade while preserving other immune functions.

Available Formulations

Guselkumab is available as a solution for subcutaneous injection in prefilled syringes and One-Press patient-controlled injector containing 100 mg/mL. The medication requires refrigeration but can be kept at room temperature (up to 77°F/25°C) for up to 30 days. Patients can self-inject after proper training.

Medical Uses

Guselkumab is FDA-approved for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, and for the treatment of adults with active psoriatic arthritis. Clinical trials demonstrated high rates of skin clearance (PASI 90, IGA 0/1) and improvement in joint symptoms. It is effective in both psoriasis and psoriatic arthritis, addressing both skin and joint manifestations.

Dosing Guidelines

For plaque psoriasis, the recommended dose is 100 mg at weeks 0 and 4, then every 8 weeks thereafter. For psoriatic arthritis, the dose is 100 mg at weeks 0 and 4, then every 8 weeks; for patients with coexistent moderate to severe plaque psoriasis, the psoriasis dosing regimen should be used. Injections may be given in the thigh, abdomen, or upper outer arm. Treatment should be discontinued if adequate response is not achieved after 16 weeks.

Important Safety Information

Guselkumab may increase the risk of infections. Patients should be evaluated for tuberculosis before initiating treatment. Treatment should not be initiated during an active infection. Patients should be instructed to seek medical attention if signs or symptoms of clinically significant infection occur. Patients should receive all recommended vaccinations before starting therapy. Live vaccines should be avoided during treatment. Hypersensitivity reactions have been reported.

Drug Interactions

No formal drug interaction studies have been conducted. Guselkumab is not expected to undergo hepatic metabolism or interact with cytochrome P450 enzymes. However, the formation of CYP450 enzymes may be normalized with IL-23 blockade; monitor CYP450 substrates with narrow therapeutic indices (e.g., warfarin, cyclosporine) and adjust doses as needed when starting or stopping guselkumab.

Special Populations

There are no adequate data on guselkumab use during pregnancy. Animal studies did not show adverse developmental effects. Use during pregnancy only if the potential benefit justifies the potential risk. It is unknown whether guselkumab is excreted in human breast milk; consider the developmental and health benefits of breastfeeding. Safety and efficacy have not been established in pediatric patients. Clinical trials included patients up to 90 years; no overall differences in safety or efficacy were observed in elderly patients. No dose adjustment is needed for renal or hepatic impairment.