Brodalumab

Mechanism of Action

Brodalumab is a human monoclonal IgG2 antibody directed at the IL-17 receptor. The IL-17 protein family is a group of six pro-inflammatory cytokines (IL17A-F) produced by T-helper cells (Th17) thought to play an important role in autoinflammatory diseases such as psoriasis, PsA, rheumatoid arthritis, and multiple sclerosis.[6] Unlike other IL-17 inhibitors, such as ixekizumab and secukinumab, which primarily target IL-17A and bind to the protein itself, brodalumab targets the IL-17RA receptor. The IL-17RA receptor is used not only by IL-17A but also by IL-17C, IL17-E, and IL-17F.  By blocking the IL-17RA receptor, brodalumab prevents the release of IL-17 mediated pro-inflammatory protein kinases and chemokines, such as nuclear factor kappa light chain enhancer of activated B cells (NF-kappa-B), IL-6, IL-8, cyclooxygenase-2 (COX-2), matrix metalloproteinases (MMPs), and granulocyte-macrophage colony-stimulating factor (GM-CSF).

Administration

Brodalumab administration is by subcutaneous injection. Patients may self-inject the 210 mg/1.5 ml prefilled syringe at weekly intervals for weeks 0, 1, and 2, followed by an injection every two weeks. Prefilled syringes should be stored at 2 degrees C to 8 degrees C but require approximately 30 minutes to reach room temperature before injection. Syringes may be stored at room temperature for up to 2 weeks but should not be re-refrigerated. If there is an inadequate response by weeks 12 to 16 of treatment, discontinue brodalumab as therapy past 16 weeks is unlikely to result in more significant disease improvement.

Adverse Effects

As brodalumab is an immune-modulating medication, most adverse reactions to therapy relate to an increased risk of infection.[7][8][9] The most common adverse events reported at week 120 of an open-label extension study in patients receiving brodalumab included:

• Nasopharyngitis (27%)
• Upper respiratory tract infections (20%)
• Arthralgia (16%)
• Back pain (11%)
• Gastroenteritis (10%)
• Influenza (9%)
• Oropharyngeal pain (9%) 
• Sinusitis (9%)

Researchers noted mild to moderate oral candidiasis in five patients (3%), and there were reports of injection site reactions in fifteen patients (8%). Additionally, a total of 15 patients (8%) reported serious adverse events. Four patients had to withdraw treatment due to infection. Transient grade-2 absolute neutrophil abnormalities occurred in four patients (2%), but all cases achieved resolution without modification in treatment. There are also several reported cases of grade-3 neutropenia.

Furthermore, while not directly establishing a causal relationship, four completed suicides, including one case ruled as indeterminate, were reported in patients receiving brodalumab during phase 3 clinical trials. Therefore, package inserts for brodalumab include a boxed warning for increased risk of suicidal ideation and behavior. Patients must be informed about this increased risk and should receive a referral to a mental health professional in the event of new or increasing thoughts of suicide or depression. Brodalumab is only available through a Risk Evaluation and Mitigation Strategy (REMS) program.

Contraindications

Inflammatory Bowel Disease

• Brodalumab is contraindicated in patients with Crohn disease. Researchers terminated a randomized, placebo-controlled trial examining the safety and efficacy of brodalumab in patients with Crohn disease due to disproportionate Crohn disease progression in those patients treated with brodalumab: 31% experienced worsening of disease versus 9% in the placebo group. Additionally, though patients with Crohn disease met the exclusion criteria from the psoriasis clinical trials, during one phase 3 study, one patient developed new-onset Crohn disease. If a patient develops Crohn disease while taking brodalumab, they should discontinue therapy.[10]

Infection

• Risks and benefits of treatment with brodalumab require thoughtful evaluation before administration in patients with chronic or recurrent infections. If a patient develops a non-resolving infection, the clinician should discontinue the medication.[11]

Children and Pregnancy

• Though no contraindication exists, researchers have not investigated the efficacy and safety of brodalumab as a potential treatment in children or pregnant women with psoriasis or breastfed infants of mothers taking brodalumab. However, monoclonal antibodies are generally known to actively be transported through the placenta, especially in the third trimester, and get excreted in modest amounts in breast milk. Risks and benefits to the mother require assessment before initiation or discontinuation of brodalumab.

Monitoring

Due to the increased risk of infection in patients prescribed brodalumab, all patients require screening for tuberculosis (TB) before initiation of the medication. If a patient has an active TB infection, the clinician should not administer the drug. For patients with latent TB or a history of latent or active TB with unconfirmed treatment, therapy for TB infection should start before the initiation of brodalumab, as there is a risk for latent TB reactivation.[12]

Patients should be informed of the increased risk of neutropenia, and they will need monitoring for any new or non-resolving infections. Additionally, live vaccines should be avoided in patients while they are taking brodalumab.

Enhancing Healthcare Team Outcomes

The management of patients with psoriasis is usually by the primary care provider, nurse practitioner, dermatologist, infectious disease consultant, internist, and rheumatologist. When the disease is moderate to severe, one option for treatment is brodalumab. This new agent was approved by the United States Food and Drug Administration for the treatment of moderate to severe plaque psoriasis in adult patients who have failed treatment with topical and other systemic therapy. The drug is effective and does provide rapid symptom relief, but monitoring of patients is necessary.

Due to the increased risk of infection in patients prescribed brodalumab, all patients require screening for tuberculosis (TB) prior to initiation of the medication. If a patient has an active TB infection, they should not receive the drug. For patients with latent TB or a history of latent or active TB with unconfirmed treatment, therapy for TB infection should start before the initiation of brodalumab, as there is a risk for latent TB reactivation.

Patients should be informed of the increased risk of neutropenia and must have ongoing monitoring for any new or non-resolving infections. Additionally, live vaccines should be avoided in patients while they are taking brodalumab. Pharmacists should carefully verify dosing and perform complete medication reconciliation for patients commencing therapy on brodalumab and report any concerns to the healthcare team. 

Nursing staff can assist in all the above monitoring activities, help evaluate ongoing treatment effectiveness, and confirm patient compliance. Should they note any issues, these must be reported to the prescribing physician immediately.

Because of its adverse event profile and potential for increased infections, brodalumab treatment requires an interprofessional team approach, including clinicians (MDs, DOs, NPs, PAs), specialists, specialty-trained nurses, and pharmacists, all collaborating across disciplines to achieve optimal patient results. After the drug is prescribed by the clinician, nursing staff should review all pertinent dosing and administration points and verify patient understanding. The pharmacist should monitor for drug-drug interactions and answer any other patient questions while reinforcing the points taught by nursing. This interprofessional approach will result in better therapeutic success with fewer adverse outcomes. [Level 5]