brodalumab

Action and Spectrum

Mechanism of action

brodalumab is a human monoclonal antibody that specifically binds to the interleukin-17 receptor (IL-17 receptor) and blocks the interaction of IL-17A, IL-17F, and IL-17A/F with the receptor. This inhibition results in a reduction of the downstream signaling events that lead to the activation of proinflammatory cytokines and chemokines

Spectrum

The spectrum of activity of brodalumab includes the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy. brodalumab has been shown to improve the signs and symptoms of plaque psoriasis, including reducing the extent and severity of skin lesions and improving quality of life

Drug Interaction

Adverse Reaction

Frequency defined:

1-10%

Arthralgia (3.3%)

Injection site reaction (1.3%)

Diarrhea (1.1%)

Nausea (1.1%)

Headache (3.5%)

Fungal infections (2.4%)

Fatigue (1.1%)

Oropharyngeal pain (1.1%)

<1%

Influenza (0.5%)

Tinea infections (0.2%)

Candida infections

Serious infections (0.5%)

Neutropenia (0.5%)

Conjunctivitis

Black Box Warning

Black box warning

brodalumab, a biological medication used for treating moderate-to-severe plaque psoriasis, carries a black box warning related to the risk of suicidal thoughts and behavior. This warning is based on clinical trial data and postmarketing reports of patients taking brodalumab who have experienced suicidal thoughts or behavior, including completed suicides

Contraindication / Caution

Contraindications

It is contraindicated in Crohn’s disease

Caution

Some of the cautions associated with brodalumab use include:

• Suicidal Ideation and Behavior: Patients treated with brodalumab should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, or any unusual changes in mood or behavior
• Cardiovascular Risks: Patients with a history of cardiovascular disease, including ischemic heart disease, peripheral vascular disease, and cerebrovascular disease, may have an increased risk of serious cardiovascular events while receiving brodalumab
• Serious Infections: brodalumab can increase the risk of serious infections, including tuberculosis, bacterial sepsis, and invasive fungal infections. Patients should be evaluated for latent or active infections before initiation of treatment
• Hypersensitivity reactions: Severe allergic reactions (anaphylaxis) have been reported with brodalumab. If symptoms of a severe allergic reaction occur, brodalumab should be discontinued immediately, and appropriate therapy initiated
• Neutralizing antibodies: The development of neutralizing antibodies to brodalumab may reduce the efficacy
• Cancer: An increased risk of malignancy has not been observed with brodalumab treatment, but a longer-term assessment is needed
• Liver tests: Increases in liver tests have been observed with brodalumab treatment
• Pregnancy and breast-feeding: It is unknown whether brodalumab is safe during pregnancy and breastfeeding. Therefore, pregnant women or those planning to become pregnant should not receive brodalumab

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available

Lactation: Excretion of the drug in human breast milk is unknown

Pregnancy category:

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology

brodalumab is a human monoclonal antibody that specifically binds to the interleukin-17 (IL-17) receptor. IL-17 is a proinflammatory cytokine that plays a vital role in developing several chronic inflammatory diseases, including psoriasis, psoriatic arthritis, and ankylosing spondylitis. By binding to the IL-17 receptor and blocking its activation, brodalumab reduces the production of proinflammatory cytokines and other mediators of inflammation

Pharmacodynamics

The pharmacodynamics of brodalumab is not fully understood, but it is believed to work by modulating the immune system to reduce inflammation and improve symptoms of chronic inflammatory diseases. Clinical trials have shown that brodalumab effectively treats psoriasis and psoriatic arthritis, improving skin clearance, joint pain and swelling, and quality of life measures

Pharmacokinetics

Absorption

It is a subcutaneously (SC) administered monoclonal antibody and has a bioavailability of approximately 55%. Its peak plasma concentration occurs around three days after administration and is approximately 13.4 mcg/mL. The area under the concentration-time curve (AUC) is estimated to be 111 mcg·day/mL.

Distribution

The apparent volume of distribution (Vd) of brodalumab is 8.9 L

Metabolism

As a human monoclonal IgG2 antibody, brodalumab is expected to be degraded into small peptides and amino acids via catabolic pathways like endogenous IgG. The metabolic pathway of brodalumab has not been characterized.

Elimination/Excretion

The total clearance of brodalumab is approximately 3 L/day

Adminstartion

Administration

It is administered as a subcutaneous (SC) injection. The recommended dose is 140 mg every two weeks, with a maximum dose of 140 mg weekly. The drug should be injected into the abdominal wall, thigh, or upper arm, and rotating the injection site can help prevent local skin reactions

Patient Information Leaflet

Patient information leaflet

Generic Name: brodalumab

Pronounced: [ broe-DAL-ue-mab ]

Why do we use brodalumab?

It is a human monoclonal antibody that targets and blocks the activity of the interleukin-17 (IL-17) receptor. It is used to treat plaque psoriasis, a chronic autoimmune skin disease, in adults who are candidates for systemic therapy or phototherapy