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February 16, 2017 – The American Food & Drug Administration (FDA) just approved Brodalumab (Siliq) to treat adults with moderate-to-severe plaque psoriasis. Brodalumab (Siliq) is administered as an injection. Brodalumab (Siliq) is intended for patients who are candidates for systemic therapy (treatment using substances that travel through the bloodstream, after being taken by mouth or injected) or phototherapy (ultraviolet light treatment) and have failed to respond, or have stopped responding to other systemic therapies.
Psoriasis is a skin condition that causes patches of skin redness and flaking. Psoriasis is an autoimmune disorder that occurs more commonly in patients with a family history of the disease, and most often begins in people between the ages of 15 and 35. The most common form of psoriasis is plaque psoriasis, in which patients develop thick, red skin with flaky, silver-white scales. Siliq’s active ingredient (brodalumab) binds to a protein that causes inflammation, inhibiting the inflammatory response that plays a role in the development of plaque psoriasis.
Brodalumab (Siliq) efficacy was established in three randomized, placebo-controlled clinical trials with a total of 4,373 adult participants with moderate-to-severe plaque psoriasis who were candidates for systemic therapy or phototherapy. More patients treated with Brodalumab (Siliq) compared to placebo had skin that was clear or almost clear, as assessed by scoring of the extent, nature and severity of psoriatic changes of the skin.
However, when looking at its safety, suicidal ideation and behavior, including completed suicides, have occurred in patients treated with Brodalumab (Siliq) during clinical trials. Brodalumab (Siliq) users with a history of suicidality or depression had an increased incidence of suicidal ideation and behavior compared to users without this history. Here, the agency claims (or perhaps, even more plausible, the applicant for market authorisation) that a causal association between treatment with Brodalumab (Siliq) and increased risk of suicidal ideation and behavior has not been established. This may be true in the strict sense that a molecular mechanism for Brodalumab (Siliq)-inducing directly completed suicide is not established. However, if already in a carefully preselected patient population of 4’373 participants in clinical trials, suicidal ideation occurs and completed suicides have occurred, there can be no question based of epidemiological evidence that Brodalumab (Siliq) causes suicidal ideation and completed suicides in that this two clinical phenotypes are much much more rare in both the general population and in the psoriasis patient population. In addition to these serious/fatal adverse effects of Brodalumab (Siliq), the most common adverse reactions reported with the use of Brodalumab (Siliq) included joint pain (arthralgia), headache, fatigue, diarrhea, throat pain (oropharyngeal pain), nausea, muscle pain (myalgia), injection site reactions, influenza, low white blood cell count (neutropenia) and fungal (tinea) infections.
Because of the observed risk of suicidal ideation and behavior, the labeling for Brodalumab (Siliq) includes a Boxed Warning and the drug is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Brodalumab (Siliq) REMS Program. Notable requirements of the Brodalumab (Siliq) REMS Program include the following:
- Prescribers must be certified with the program and counsel patients about this risk. 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 behavior, feelings of depression, anxiety or other mood changes.
- Pharmacies must be certified with the program and must only dispense to patients who are authorized to receive Brodalumab (Siliq).
Brodalumab (Siliq) is also approved with a Medication Guide to inform patients of the risk of suicidal ideation and behavior, and that because Brodalumab (Siliq) is a medication that affects the immune system, patients may have a greater risk of getting an infection, or an allergic or autoimmune condition. Patients with Crohn’s disease should not use Brodalumab (Siliq). Health care providers should also evaluate patients for tuberculosis (TB) infection prior to initiating treatment with Brodalumab (Siliq). Health care providers should not administer Brodalumab (Siliq) to patients with active TB infection, and should avoid immunizations with live vaccines in patients being treated with Brodalumab (Siliq).
Overall, in this particular case, one has really to question the risk/benefit ratio that has led FDA to approve Brodalumab (Siliq) in the first place, at how the agency could probably put so many psoriasis patient at a fatal risk? There is no antidote for completed suicide, remember.