In February 2017, the biological treatment brodalumab (Siliq™; Valeant Pharmaceuticals, New Jersey, USA) received US Food and Drug Administration (FDA) approval to treat psoriasis in adult patients who have not responded to other treatments.
Valeant expects to commence sales and marketing of brodalumab in the United States in the second half of 2017.
Because of the observed risk of suicidal ideation and behaviour, the labelling for brodalumab includes a boxed warning and the drug is only available through a restricted programme under the FDA’s Risk Evaluation and Mitigation Strategies (REMS) Program. Notable requirements of the programme are included below.
- Prescribers must be certified with the REMS Program and counsel patients about the risk of suicidal ideation and behaviour.
- Patients with new or worsening symptoms of depression or suicidality should be referred to a mental health professional as appropriate.
- Patients must sign a patient–prescriber agreement form and be made aware of the need to seek medical attention should they experience new or worsening suicidal thoughts or behaviour, feelings of depression, anxiety or other mood changes.
- Pharmacies must also be certified with the REMS Program and must only dispense brodalumab to patients who are authorised to receive the medication.
A causal association between treatment with brodalumab and the increased risk of suicidal ideation and behaviour has not been established.
Chronic plaque psoriasis
What is brodalumab used for?
Brodalumab is used for the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy and have failed to respond, or have stopped responding to other systemic therapies.
It is recommended for candidates for whom systemic therapy or phototherapy have failed to provide results or adequate treatment.
How does brodalumab work?
Brodalumab is a monoclonal immunoglobulin G2 (IgG2) antibody that inhibits inflammatory reactions and selectively binds to the receptor of interleukin 17 (IL-17), a cytokine that initiates inflammation.
The IL-17 receptor is a protein expressed on the cell surface and is a component of receptor complexes used by multiple IL-17 family cytokines, such as IL-17A, IL-17F, IL-17C, IL-17A/F heterodimer, and IL-25. Blocking the IL-17 receptor inhibits IL-17 cytokine-induced responses, including the release of proinflammatory cytokines and chemokines associated with the pathogenesis of psoriasis.
How is brodalumab administered?
Brodalumab is administered subcutaneously. Each prefilled syringe (1.5 mL) contains 210 mg of brodalumab and is for single-use only.
- The recommended dose for brodalumab 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 12–16 weeks of treatment, brodalumab therapy should be discontinued.
- Brodalumab should not be injected into areas where the skin is tender, bruised, red, hard, thick, scaly, or affected by psoriasis.
- Brodalumab is contraindicated in patients with Crohn disease because the drug can cause worsening of the disease.
- Patients with a history of latent tuberculosis should be treated prior to administration of brodalumab, which can reactivate latent tuberculosis infection.
The use of brodalumab in specific populations
There are no data available on the use of brodalumab in pregnant women to inform physicians of a drug-associated risk for major birth defects and miscarriage.
No adverse developmental effects have been observed in pregnant monkeys after subcutaneous administration of brodalumab at up to 26 times the maximum recommended dose for humans. (See Safety of medicines taken during pregnancy for more information.)
There is no information on the presence of brodalumab in human milk or its effects on the breastfed infant. The risk–benefit potential should be considered when prescribing brodalumab to a lactating mother. (See Lactation and medications used in dermatology).
The safety and effectiveness of brodalumab have not been evaluated in paediatric patients.
Clinical studies with brodalumab did not include sufficient numbers of subjects aged 65 years and over to determine whether older people will respond differently from younger individuals.
Individuals with hepatic or renal impairment
No trials have been conducted to assess the use of brodalumab in patients with hepatic or renal impairment.
What are the risks with brodalumab?
The most common adverse reactions (≥ 1% of patients) reported with brodalumab include:
- Arthralgia (joint pain)
- Oropharyngeal pain (throat pain)
- Myalgia (muscle pain)
- Injection site reactions
- Neutropenia (low white-blood-cell count)
- Fungal infections (such as tinea).
The following serious adverse reactions have been reported in clinical trials in patients treated with brodalumab:
- Suicidal ideation and behaviour
- Serious infections such as cryptococcal meningitis
- Latent tuberculosis reactivation
- Exacerbation of Crohn disease.
There are no data available on the ability of live or inactive vaccines to elicit an immune response in patients receiving treatment with brodalumab. Live vaccines should not be used during brodalumab treatment.
The effect of drugs metabolised via the hepatic cytochrome P450 enzymes (such as warfarin and ciclosporin) may be altered during concurrent administration with brodalumab. The modification of the dosages of these drugs should be considered.
Brodalumab is contraindicated in individuals who:
- Have a history of mental problems, including suicidal thoughts, depression, anxiety, or mood problems
- Have recurring infections
- Have tuberculosis or have been in close contact with someone with tuberculosis
- Have recently received, or are scheduled to receive, a vaccine
- Plan to become pregnant
- Are currently breastfeeding or plan to breastfeed.
What is the outlook for treatment with brodalumab?
Brodalumab has shown an acceptable safety profile and good efficacy in the treatment of moderate-to-severe plaque psoriasis. It provides an important new therapy in the management of psoriasis where there remains a significant unmet need for new agents with novel mechanisms of action, rapid onset of effect, and improved and sustained total skin clearance while aiding greater patient adherence and minimising drug-specific safety concerns.
However, the current evidence for brodalumab is insufficient to confirm the maintenance of these results in the long term.
We suggest you refer to your national drug approval agency such as the Australian Therapeutic Goods Administration (TGA), US Food and Drug Administration (FDA), UK Medicines and Healthcare products regulatory agency (MHRA) / emc, and NZ Medsafe, or a national or state-approved formulary eg, the New Zealand Formulary (NZF) and New Zealand Formulary for Children (NZFC) and the British National Formulary (BNF) and British National Formulary for Children (BNFC).