Drug Name: Brodalumab

Brand Name: SILIQ

Manufacturer: Valeant Pharmaceuticals

Primary Indications: Resistant cases of severe plaque psoriasis

SILIQ (Brodalumab) is a human monoclonal antibody that targets Interleukin 17. It binds to cells that express IL-17RA and inhibits the functions of IL-17 and IL-25. It has been approved for the treatment of moderate to severe plaque psoriasis which has failed to respond to other systemic therapies and those who are candidates for phototherapy [Ref].

SILIQ (Brodalumab) Injection Dosage And Administration

Dosage:

• SILIQ is administered in a dose of 210 mg subcutaneously weekly for the first three weeks (weeks 0, 1, and 2) and then every two weeks.
• If no significant response is noted within 12 - 16 weeks, the treatment is discontinued.

Instructions for administering SILIQ:

• The injection is to be administered only into the skin (subcutaneously). Administering it intravenously, intramuscularly, or into the skin that is bruised, infected, or tender should be avoided.
• The injection is intended for single use only. Patients may need training before injecting it themselves.

Preparing SILIQ injection:

• Allow the injection to warm at room temperature after taking it out from the refrigerator.
• It may take about 30 minutes.
• Do not warm the prefilled syringe in any other way.
• Do not remove the gray needle cap until you are ready to inject it.

Visual Inspection

• Inspect the injection for particles and discoloration. It should be clear to slightly opalescent, colorless to slightly yellow solution.
• The presence of a few translucent to white, amorphous proteinaceous particles is normal. But if the injection is cloudy or discolored or it contains any foreign particles should not be used.

Instructions for Use

• Patients should inject the whole volume of the injection containing 210 mg per 1.5 ml of the solution.
• Detailed instructions on how to correctly inject SILIQ are available in the Instructions for Use.

SILIQ (Brodalumab) Contraindications:

Avoid SILIQ injection in patients with Crohn's disease. It may result in a flare-up of the symptoms of Crohn's disease.

Warnings and Precautions:

• Increased risks of Suicidal thoughts and Behavior:

Although it is not very clear why patients are at risk of developing suicidal thoughts, a significant number of patients developed suicidal thoughts and some did suicide and died.

Patients who have a history of depression are greatly at increased risk of suicidal tendencies. The manufacturer recommends screening for underlying depression and mental issues. Patients on treatment should be periodically assessed for suicidal behaviors and those with new-onset symptoms should be asked to discontinue the treatment.

SILIQ treatment should be avoided in patients who are at risk of suicide. In addition, treatment should not be unnecessarily prolonged beyond 16 weeks especially if no meaningful response is achieved.

A restricted program under a REMS is in place for the distribution of SILIQ. This program has made it mandatory for prescribers to get trained and obtain certification in the SILIQ REMS program.

In addition, patients must sign an agreement form before they are prescribed the injection. Lastly, only pharmacies that have been authorized can dispense the drug.

• Infections:

Brodalumab is an immune modulator. There is an increased risk of serious infections during the treatment. Patients should be asked to report any sign of an infection earlier.

During clinical trials, one patient developed a CNS infection (cryptococcal meningitis).

• Risk for Latent Tuberculosis Reactivation

Test all patients for latent TB infection. It is contraindicated in active TB infection. Patients who are diagnosed as having latent TB should complete their course of treatment before they are prescribed Brodalumab. 

In addition, TB treatment should also be considered for those with a history of TB. All patients should be kept under surveillance for developing TB during the treatment.

• Crohn's Disease

SILIQ is contraindicated in patients with Crohn's disease as it may worsen the underlying symptoms of Crohn's disease. In clinical trials, one patient developed Crohn's disease during SILIQ treatment.

• Immunizations

Patients should avoid live vaccines during the treatment.

Side Effects of Brodalumab Vs Stelara in clinical trials:

Immunogenicity of SILIQ:

SILIQ, a therapeutic protein, has the potential for immunogenicity, which can lead to antibody formation in patients. However, the antibodies that were detected were not neutralizing antibodies and hence it is less likely to alter the efficacy of the drug.

Brodalumab Drug Interaction:

Live Vaccinations:

• Patients receiving SILIQ treatment should avoid using live vaccines.

CYP450 Substrates

• Chronic inflammation can increase certain cytokines like IL-1, IL-6, IL-10, TNFα, IFN, and alter CYP450 enzyme formation.
• SILIQ treatment can modulate serum levels of cytokines, hence monitoring the effects of SILIQ is recommended upon initiation or discontinuation of treatment in patients on concomitant drugs that are CYP450 substrates.
• Monitoring is especially important for drugs with a narrow therapeutic index where the patient is prone to develop side effects very rapidly.
• Monitor INR in patients on warfarin and drug levels in patients using cyclosporin. For other drugs that are CYP450 substrates, adjustment in the dose may be required.

Use in specific populations

Pregnancy

• SILIQ use in pregnant women is not supported by human data.
• Human IgG antibodies can cross the placental barrier, which may result in SILIQ transmission to the fetus. However, in animal studies the use of Brodalumab at doses of 26 times the normal dose did not result in any side effects in the infants.

Breastfeeding:

• Data is limited but since IgG can cross into the breast milk, breastfeeding should be stopped or the treatment should be discontinued.

Use in Children:

• Not studied in children and hence not recommended.

Use in older people above 65 years of age:

• No significant change in efficacy or side effects was observed in clinical trials in older people compared to younger people.

Mechanism of Action of Brodalumab:

Brodalumab is a human monoclonal IgG2 antibody that selectively binds to cells expressing human IL-17RA. 

Inhibiting IL-17 and IL-25 results in the inhibition of the immune cascade and formation of pro-inflammatory cytokines and chemokines which play a significant role in the development of psoriasis and psoriatic arthritis.

Administration: subcutaneous

Peak serum concentration: 3 days after injection

Steady-state concentration: achieved within 4 weeks

Bioavailability: 55%

Elimination: catabolism into peptides

SILIQ Patient information:

Storage and Handling

• Keep SILIQ refrigerated at a temperature range of 2°C to 8°C (36°F to 46°F)
• The prefilled syringes can be stored at room temperature for a maximum of 14 days and discarded after 14 days. Do not refrigerate it once the injection has been kept at room temperature.
• Avoid exposing the injections to the sun exposure.
• Do not freeze or shake the syringe.

Reading FDA-Approved

• Patients should read the FDA-prescribing labels

Suicidal Thoughts and Risks:

• Patients should report changes in mood when started on treatment and seek medical advice.
• Physicians and pharmacies should be certified in the REMS program and patients enrolled in the REMS program can only get the treatment.

Infections

• The immunity of the patient may drop with the injections and the patient may become prone to infections.
• Patients must notify their doctors if they get an infection even if it's milder in nature.

Crohn’s Disease

• Patients should notify their doctors if they develop diarrhea or if have blood in stools associated with abdominal pain. These symptoms may be suggestive of Crohn's disease.

Instructions for Injection

• Patients must be trained regarding the proper administration of the injection and disposal of the syringe.