Psoriasis, a chronic autoimmune disease characterized by thick, inflamed patches of skin, affects approximately 7.5 million people in the United States.1 Plaque psoriasis is the most common form of psoriasis, affecting 80% to 90% of patients with the disease.2 Plaque psoriasis is characterized by raised, red patches covered with a scaly accumulation of dead skin cells.3 Complex medical care is often required to treat the pruritus, pain, and, sometimes, bleeding of psoriatic patches.1 For some patients, psoriasis can lead to disfigurement and disability.1
Patients with psoriasis are at increased risk for psoriatic arthritis, heart disease, stroke, hypertension, type 2 diabetes, metabolic syndrome, eye disorders, and obesity, as well as for other autoimmune diseases (eg, celiac disease, Crohn’s disease), Parkinson’s disease, and kidney disease.3
Psoriasis substantially affects a patient’s quality of life and self-esteem and can lead to social isolation.3,4 In addition, the majority of patients with psoriasis regularly experience pain and pruritus.4 Individuals with psoriasis are also at increased risk for depression, anxiety, and suicidality.5
Interleukin (IL)-17 cytokines play a role in activating inflammation in the pathogenesis of psoriasis.6,7 The IL-17 receptor A (IL-17RA) antagonists, a relatively new class of drugs in the treatment of plaque psoriasis, target the IL-17 pathway.8,9
Brodalumab Receives FDA Approval for Plaque Psoriasis
On February 15, 2017, brodalumab (Siliq; Valeant Pharmaceuticals), a human IL-17RA antagonist, was approved by the US Food and Drug Administration (FDA) for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy, and whose disease had an inadequate response to or stopped responding to other systemic therapies.10,11
“Moderate-to-severe plaque psoriasis can cause significant skin irritation and discomfort for patients, and today’s approval provides patients with another treatment option for their psoriasis. Patients and their health care providers should discuss the benefits and risks of Siliq before considering treatment,” said Julie Beitz, MD, Director of the FDA’s Office of Drug Evaluation III.11
Because of the reported risk for suicidal ideation and behavior, brodalumab is only available through specialty pharmacies authorized to fill prescriptions under a Risk Evaluation and Mitigation Strategy (REMS) program—the Siliq REMS Program.11,12
Mechanism of Action
Brodalumab is a human monoclonal immunoglobulin G2 antibody that is selectively binding to human IL-17RA, thereby inhibiting brodalumab’s interaction with several cytokines, including IL-17A, IL-17F, IL-17C, IL-17A/F heterodimer, and IL-25. The IL-17RA protein plays a key role in the binding and downstream signaling of multiple IL-17 cytokines.10,13 By blocking IL-17RA, brodalumab inhibits IL-17 cytokine-induced responses, including the release of proinflammatory cytokines and chemokines implicated in the development of plaque psoriasis.10,11
Dosing and Administration
Brodalumab 210 mg is administered as a subcutaneous injection at weeks 0, 1, and 2, followed by 210 mg every 2 weeks. The brodalumab injection is available as a 210-mg/1.5-mL solution in a single-dose prefilled syringe.10
Phase 3 Clinical Trials
The safety and efficacy of brodalumab were established in 3 randomized, double-blind, controlled phase 3 clinical trials—AMAGINE-1, -2, and -3.6,10,13 These studies included 4373 adults (mean age, 45 years) with a ≥6-month history of moderate-to-severe plaque psoriasis. Approximately 21% of patients had a history of psoriatic arthritis, 30% previously received a biologic therapy, and 12% did not respond to previous biologic therapy.6,10,13
Results from these 3 trials are shown in the Table. Up to 86% of patients receiving brodalumab showed a 75% reduction in Psoriasis Area and Severity Index (PASI) score; up to 80% showed a static Physician’s Global Assessment (sPGA) score 0 (clear) or 1 (almost clear); and up to 45% showed an sPGA score 0.6,10,13
In studies 2 and 3, approximately twice as many patients receiving brodalumab 210 mg every 2 weeks achieved a 100% reduction in PASI score compared with patients receiving ustekinumab (Stelara).10,13 Ustekinumab is a human IL-12 and IL-23 antagonist approved by the FDA for the treatment of patients with moderate-to-severe plaque psoriasis.14 In addition, at week 12, more patients in the brodalumab 210-mg arm achieved a Psoriasis Symptom Inventory score 0 (not at all) or 1 (mild) on every item, including itch, redness, scaling, burning, stinging, cracking, flaking, and pain, than patients in the placebo group.10,13
During the 12-week randomized induction treatment of the pooled clinical trials, the most common adverse events occurring with brodalumab at a rate of ≥1% (and higher than with placebo) included arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection-site reactions, influenza, neutropenia, and tinea infections.6,10,13 Adverse events that led to brodalumab discontinuation included neutropenia, arthralgia, and urticaria.10
As with other therapeutic proteins, immunogenicity may occur with brodalumab. Through the 52-week treatment duration, approximately 3% of patients receiving brodalumab developed antibodies to the drug.10,13
Brodalumab is contraindicated in patients with Crohn’s disease.10
Brodalumab may modulate the serum levels of some cytokines. When brodalumab is initiated or discontinued in patients receiving concomitant drugs that are cytochrome (CY) P450 substrates, particularly those with a narrow therapeutic index, monitoring for effect (eg, for warfarin) or drug concentration (eg, for cyclosporine) should be considered, and dose modification of CYP450 substrate may be needed.10
Warnings and Precautions
Brodalumab was approved with a boxed warning about the potential risk for suicidal ideation and behavior, including completed suicides, associated with brodalumab. The risks and benefits in patients with a history of depression and/or suicidal ideation or behavior should be weighed carefully before prescribing the drug. Patients with suicidal thoughts and behavior should be referred to a mental health professional.10
Brodalumab may increase the risk for infections, including serious infections. If a serious infection occurs, brodalumab should be discontinued until the infection resolves.10
Patients should be evaluated for tuberculosis infection before starting brodalumab treatment.10
Crohn’s disease and exacerbation of Crohn’s disease were reported in clinical trials of brodalumab. Brodalumab therapy should be discontinued if Crohn’s disease is diagnosed while taking the drug.10
Live vaccines should not be administered during brodalumab treatment.10
Use in Specific Populations
No human data are available on the risks associated with brodalumab in pregnant women.10
No data are available on the presence of brodalumab in human milk, or of the drug’s effects on breastfed infants or milk production. The benefits of breastfeeding and the mother’s need for brodalumab should be weighed against any potential adverse effects on the infant from brodalumab or the mother’s underlying condition.10
No differences in safety or efficacy were observed between patients aged ≥65 years and younger patients; however, the number of older patients was insufficient to establish any potential differences in response.10
The safety and efficacy of brodalumab in pediatric patients have not been established.10
The FDA approval of brodalumab provides another treatment option for patients with moderate-to-severe plaque psoriasis. The dosing schedule for brodalumab and its availability as a single-use, prefilled syringe may provide appropriate patients with a convenient disease management option.
- National Psoriasis Foundation. Psoriasis and comorbid conditions issue brief. www.psoriasis.org/sites/default/files/advocacy/PsoriasisandComorbidConditionsIssueBriefonepager20140225.pdf. Accessed May 23, 2017.
- Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008;58:826-850.
- Mayo Clinic staff. Diseases and conditions: psoriasis. May 12, 2017. www.mayoclinic.org/diseases-conditions/psoriasis/home/ovc-20317577. Accessed May 22, 2017.
- Armstrong AW, Schupp C, Wu J, Bebo B. Quality of life and work productivity impairment among psoriasis patients: findings from the National Psoriasis Foundation survey data 2003-2011. PLoS One. 2012;7:e52935.
- Kurd SK, Troxel AB, Crits-Christoph P, Gelfand JM. The risk of depression, anxiety, and suicidality in patients with psoriasis: a population-based cohort study. Arch Dermatol. 2010;146:891-895.
- Papp KA, Reich K, Paul C, et al. A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. Br J Dermatol. 2016;175:273-286.
- Fitch E, Harper E, Skorcheva I, et al. Pathophysiology of psoriasis: recent advances on IL-23 and Th17 cytokines. Curr Rheumatol Rep. 2007;9:461-467.
- Cosentyx (secukinumab) injection [prescribing information]. East Hanover, NJ: Novartis; January 2016.
- Taltz (ixekizumab) injection [prescribing information]. Indianapolis, IN: Eli Lilly; January 2017.
- Siliq (brodalumab) injection [prescribing information]. Bridgewater, NJ: Valeant Pharmaceuticals North America; February 2017.
- US Food and Drug Administration. FDA approves new psoriasis drug. Press release. February 15, 2017. www.fda.gov/newsevents/newsroom/pressannouncements/ucm541981.htm. Accessed May 18, 2017.
- Siliq REMS Program. Siliq certified pharmacy network. June 15, 2017. https://siliqrems.com/SiliqUI/certificationLookup.u. Accessed September 8, 2017.
- Lebwohl M, Strober B, Menter A, et al. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N Engl J Med. 2015;373:1318-1328.
- Stelara (ustekinumab) injection [prescribing information]. Horsham, PA: Janssen Biotech; September 2016.