Brodalumab
Introduction to Brodalumab
Brodalumab is a fully human monoclonal antibody that targets the interleukin-17 receptor A (IL-17RA). It belongs to the class of biologic drugs known as IL-17 inhibitors. Brodalumab was developed for the treatment of moderate to severe plaque psoriasis and is also being studied for other inflammatory conditions.
The drug was approved by the U.S. Food and Drug Administration (FDA) in 2017 under the brand name Siliq™ 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.
Mechanism of Action
Brodalumab exerts its therapeutic effects through the following mechanisms:
- IL-17 Receptor Blockade: Brodalumab binds with high affinity to the IL-17RA, effectively blocking the biological activity of pro-inflammatory cytokines IL-17A, IL-17F, IL-17A/F heterodimer, and IL-25 (IL-17E).
- Inhibition of Inflammatory Cascade: By blocking IL-17 signaling, brodalumab disrupts the inflammatory cascade involved in the pathogenesis of psoriasis and other inflammatory conditions.
- Reduction of Keratinocyte Proliferation: IL-17 is known to stimulate keratinocyte proliferation and activation. By inhibiting IL-17 signaling, brodalumab helps normalize keratinocyte proliferation in psoriatic lesions.
- Modulation of Gene Expression: Brodalumab treatment leads to the normalization of gene expression profiles associated with the pathogenesis of psoriasis.
Indications
Brodalumab is primarily indicated for:
- 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.
While not yet approved for pediatric use, clinical trials are ongoing to evaluate its safety and efficacy in children and adolescents with moderate to severe plaque psoriasis. Other potential indications being studied include:
- Psoriatic arthritis
- Axial spondyloarthritis
- Atopic dermatitis
Dosage and Administration
For adult patients with moderate to severe plaque psoriasis:
- The recommended dose is 210 mg administered by subcutaneous injection at Weeks 0, 1, and 2 followed by 210 mg every 2 weeks.
- If an adequate response has not been achieved after 12 to 16 weeks of treatment, consider discontinuing therapy.
- Brodalumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after proper training in subcutaneous injection technique.
Pediatric dosing:
As of 2024, brodalumab is not approved for use in pediatric patients. Clinical trials are ongoing to establish appropriate dosing regimens for children and adolescents with moderate to severe plaque psoriasis.
Adverse Effects
Common adverse reactions (incidence ≥ 1%) associated with brodalumab include:
- Arthralgia (joint pain)
- Headache
- Fatigue
- Diarrhea
- Oropharyngeal pain
- Nausea
- Myalgia (muscle pain)
- Injection site reactions (erythema, pain, pruritus, bruising, hemorrhage)
- Influenza
- Neutropenia
- Tinea infections (fungal infections)
Serious adverse effects:
- Suicidal ideation and behavior: Brodalumab has a boxed warning for suicidal ideation and behavior. Patients should be monitored for onset or worsening of depression, suicidal thoughts, or behavior.
- Infections: Brodalumab may increase the risk of infections. Caution should be exercised when considering the use of brodalumab in patients with chronic or recurrent infections.
- Crohn's Disease: Exacerbations of Crohn's disease have been observed in clinical trials. Patients with active Crohn's disease should not be treated with brodalumab.
Precautions and Contraindications
Contraindications:
- Known hypersensitivity to brodalumab or any of its excipients
- Active Crohn's disease
Precautions:
- Suicidal Ideation and Behavior: Patients should be assessed for depression and suicidal ideation before starting treatment. If a patient develops new or worsening depression, anxiety, or suicidal thoughts, consider discontinuing brodalumab.
- Infections: Evaluate patients for tuberculosis (TB) infection prior to initiating treatment. Do not administer brodalumab to patients with active TB infection. Exercise caution when considering brodalumab for patients with chronic or recurrent infections.
- Vaccinations: Avoid using live vaccines concurrently with brodalumab. Non-live vaccinations received during brodalumab treatment may not elicit an immune response sufficient to prevent disease.
- Inflammatory Bowel Disease: Monitor patients for signs and symptoms of inflammatory bowel disease. If IBD occurs, discontinue brodalumab treatment.
- Pregnancy and Lactation: Limited data are available on the use of brodalumab in pregnant women. It is not known whether brodalumab is excreted in human milk. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for brodalumab.
- Pediatric Use: Safety and efficacy have not been established in pediatric patients. Clinical studies are ongoing.
- Geriatric Use: No overall differences in safety or efficacy were observed between older and younger adult patients. However, the number of patients aged 65 years and older in clinical trials was limited.
