Brodalumab

• Plaque Psoriasis
• Moderate to Severe Psoriasis
• Biologic Psoriasis Treatment
• IL-17 Pathway Blockade

Brodalumab is a fully human monoclonal antibody that targets interleukin-17 receptor A (IL-17RA) for the treatment of moderate to severe plaque psoriasis. This biologic medication provides a unique mechanism by blocking the receptor rather than the cytokine itself.

Mechanism of Action

Brodalumab is an IgG2 monoclonal antibody that selectively binds to human interleukin-17 receptor A (IL-17RA) and inhibits its interaction with multiple IL-17 cytokines (IL-17A, IL-17F, IL-17C, IL-17E/IL-25, and IL-17A/F heterodimer). The IL-17 pathway plays a critical role in psoriasis pathogenesis by promoting keratinocyte proliferation and inflammatory responses. By blocking the receptor rather than individual cytokines, brodalumab provides comprehensive inhibition of IL-17 signaling. This results in reduced inflammation, decreased keratinocyte proliferation, and normalization of skin.

Available Formulations

Brodalumab is available as a solution for subcutaneous injection in single-dose prefilled syringes containing 210 mg/1.5 mL. The medication requires refrigeration and should be brought to room temperature before administration. Patients can self-administer after proper training.

Medical Uses

Brodalumab is FDA-approved for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. It is only available through a restricted Risk Evaluation and Mitigation Strategy (REMS) program due to suicidal ideation and behavior concerns. Clinical trials demonstrated high rates of skin clearance, with many patients achieving PASI 75, 90, or 100 responses.

Dosing Guidelines

The recommended dose is 210 mg administered subcutaneously at weeks 0, 1, and 2, followed by 210 mg every 2 weeks thereafter. Injection sites include the thigh, abdomen, or upper arm. Injection sites should be rotated, and injections should not be given into areas of skin affected by psoriasis. If adequate response is not achieved after 12-16 weeks, discontinuation should be considered. Treatment should be discontinued if a patient experiences suicidal ideation or behavior.

Important Safety Information

Brodalumab carries a boxed warning regarding suicidal ideation and behavior, including completed suicides, observed in clinical trials. It is available only through a REMS program, and prescribers must be certified and patients must sign a Patient-Prescriber Agreement Form. The medication should be discontinued if new or worsening suicidal thoughts occur. Other risks include serious infections (avoid initiating during active infections), Crohn's disease, and hypersensitivity reactions. Patients should complete all immunizations before starting therapy.

Drug Interactions

No formal drug interaction studies have been conducted with brodalumab. Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation. As brodalumab modulates IL-17 signaling, the formation of CYP450 enzymes could be normalized. Monitor patients receiving concomitant CYP450 substrates with narrow therapeutic indices (warfarin, cyclosporine) and consider dose adjustments as needed.

Special Populations

There are no adequate data on brodalumab use in pregnant women. Animal studies showed no evidence of fetal harm. It is unknown whether brodalumab is excreted in human breast milk; the benefits of breastfeeding should be considered along with the importance of the medication to the mother. Safety and efficacy have not been established in pediatric patients. Clinical trials included patients up to 75 years; no overall differences in safety or efficacy were observed in elderly patients. No dose adjustment is needed for renal or hepatic impairment.