Approval Status: Approved January 2017
Specific Treatments: facial erythema associated with rosacea
Therapeutic Areas Dermatology
Siliq (brodalumab) is a human interleukin-17 receptor A (IL-17RA) antagonist.
Siliq is specifically indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies.
Siliq is supplied as an injection for subcutaneous administration. The recommended dose 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 to 16 weeks of treatment with Siliq, consider discontinuing therapy. Continued treatment beyond 16 weeks in patients who have not achieved an adequate response is not likely to result in greater success.
The FDA approval of Siliq was based on three randomized, placebo-controlled clinical trials with a total of 4,373 adults with moderate-to-severe plaque psoriasis who were candidates for systemic therapy or phototherapy. In all three trials, subjects were randomized to subcutaneous treatment with placebo or Siliq 210 mg at Weeks 0, 1, and 2, followed by treatments every 2 weeks [Q2W] through Week 12. In the two active comparator trials (Trials 2 and 3), subjects randomized to ustekinumab received a 45 mg dose if their weight was less than or equal to 100 kg and a 90 mg dose if their weight was greater than 100 kg at Weeks 0, 4, and 16, followed by the same dose every 12 weeks. All three trials assessed the change from baseline to Week 12 compared to placebo in the two co-primary endpoints: 1) PASI 75, the proportion of subjects who achieved at least a 75% reduction in the PASI composite score that takes into consideration both the percentage of body surface area affected and the nature and severity of psoriatic changes (induration, erythema, and scaling) within the affected region, and 2) the proportion of subjects with an sPGA of 0 (clear) or 1 (almost clear), and at least a 2-point improvement from baseline. In Trials 2 and 3, comparisons were also made to ustekinumab for the primary endpoint of the proportion of subjects who achieved a reduction in PASI score of 100% (PASI 100) from baseline at Week 12. Results are as follows:
PASI 75 response: Siliq 83% versus placebo 6%; sPGA of 0 (clear) or 1 (almost clear): Siliq 76% versus placebo 1%
PASI 75 response: Siliq 86% versus Ustekinumab 70% versus placebo 8%; sPGA of 0 (clear) or 1 (almost clear): SIliq 79% versus Ustekinumab 61% versus placebo 4%; PASI 100 response: Siliq 44% versus Ustekinumab 22% versus placebo 1%
PASI 75 response: Siliq 85% versus Ustekinumab 69% versus placebo 6%; sPGA of 0 (clear) or 1 (almost clear): Siliq 80% versus Ustekinumab 57% versus placebo 4%; PASI 100 response: Siliq 37% versus Ustekinumab 19% versus placebo <1%
Adverse effects associated with the use of Siliq may include, but are not limited to, the following:
- oropharyngeal pain
- injection site reactions
- tinea infections
Serious infections have occurred with the use of Siliq. Consider the risks and benefits prior to initiating Siliq in patients with a chronic infection or a history of recurrent infection.
Siliq comes with a the following Black Box warning:
Suicidal ideation and behavior, including completed suicides, have occurred in patients treated with Siliq. Prior to prescribing, weigh potential risks and benefits in patients with a history of depression and/or suicidal ideation or behavior. Patients with new or worsening suicidal thoughts and behavior should be referred to a mental health professional, as appropriate. Advise patients and caregivers to seek medical attention for manifestations of suicidal ideation or behavior, new onset or worsening depression, anxiety, or other mood changes. Siliq is available only through a restricted program called the Siliq REMS Program.
Mechanism of Action
Siliq (brodalumab) is a human monoclonal IgG2 antibody that selectively binds to human IL-17RA and inhibits its interactions with cytokines IL-17A, IL-17F, IL-17C, IL-17A/F heterodimer and IL-25. IL-17RA is a protein expressed on the cell surface and is a required component of receptor complexes utilized by multiple IL-17 family cytokines. Blocking IL 17RA inhibits IL-17 cytokine-induced responses including the release of pro-inflammatory cytokines and chemokines.
For additional information regarding Siliq or plaque psoriasis, please visit http://www.valeant.com/