Dosage & administration
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Siliq prescribing information
5.2)
SILIQ
®(brodalumab) is 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.
Administer 210 mg of SILIQ by subcutaneous injection at Weeks 0, 1, and 2 followed by 210 mg every 2 weeks. (
2.2)
Injection: 210 mg/1.5 mL solution in a single-dose prefilled syringe. SILIQ is a clear to slightly opalescent, colorless to slightly yellow solution.
There are no human data on SILIQ use in pregnant women to inform a drug-associated risk. Human IgG antibodies are known to cross the placental barrier; therefore, SILIQ may be transmitted from the mother to the developing fetus. In a combined embryofetal development and pre- and postnatal development study, no adverse developmental effects were observed in infants born to pregnant monkeys after subcutaneous administration of brodalumab during organogenesis through parturition at doses up to 26 times the maximum recommended human dose (MRHD)
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
A combined embryofetal development and pre- and postnatal development study was conducted in cynomolgus monkeys administered brodalumab. No brodalumab-related effects on embryofetal toxicity or malformations, or on morphological, functional, or immunological development were observed in infants from pregnant monkeys administered weekly subcutaneous doses of brodalumab up to 26 times the MRHD from the beginning of organogenesis to parturition (on a mg/kg basis of 90 mg/kg/week).
- Crohn’s disease because SILIQ may cause worsening of disease [see Warnings and Precautions (
)]. - Clinically significant hypersensitivity to brodalumab or to any of the excipients in SILIQ or component of the container. Hypersensitivity reactions, including anaphylaxis, have been reported with postmarket use of SILIQ [see Warnings and Precautions (
5.3)].
- Hypersensitivity Reactions:Serious hypersensitivity reactions, including anaphylaxis, may occur. If a serious hypersensitivity reaction occurs, immediately discontinue SILIQ and initiate appropriate therapy. (
5.3) - Infections:Serious infections have occurred. Consider the risks and benefits prior to initiating SILIQ in patients with a chronic infection or a history of recurrent infection. Instruct patients to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a serious infection develops, discontinue SILIQ until the infection resolves. (
5.4) - Tuberculosis (TB):Evaluate patients for TB infection prior to initiating treatment with SILIQ. (
5.5) - Eczematous Eruptions:The onset of eczematous eruptions was variable, ranging from days to months after the first dose of SILIQ. Some cases of severe eczematous eruptions resulted in hospitalization. Treatment may need to be discontinued to resolve the eczematous eruption. Some patients with limited psoriasis treatment options were successfully treated for eczema while continuing SILIQ. (
5.6) - Crohn’s Disease:Crohn’s disease occurred during clinical trials. Discontinue SILIQ if patient develops Crohn’s disease while taking SILIQ. (
) - Immunizations:Avoid using live vaccines concurrently with SILIQ. (
)
The following serious adverse reactions are discussed in greater detail in other sections of labeling:
- Suicidal Ideation and Behavior
- Hypersensitivity Reactions
- Infections [
- Crohn’s Disease
The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNFα, IFN) during chronic inflammation. Treatment with SILIQ may modulate serum levels of some cytokines.
Therefore, upon initiation or discontinuation of SILIQ in patients who are receiving concomitant drugs which are CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for effect (e.g., for warfarin) or drug concentration (e.g., for cyclosporine) and consider dosage modification of the CYP450 substrate
Brodalumab is a human monoclonal IgG2κ antibody directed against human interleukin-17 receptor A (IL-17RA). It is expressed in a Chinese Hamster Ovary (CHO) cell line. Brodalumab is comprised of 1312 amino acids and has an estimated molecular mass of 144,000 Daltons.
SILIQ (brodalumab) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution delivered via subcutaneous injection. SILIQ is supplied in a single-dose syringe made from type 1 glass with stainless steel 27G x ½” needle. Each SILIQ single-dose prefilled syringe delivers 1.5 mL of solution containing 210 mg of brodalumab formulated in glutamate (6.5 mg), polysorbate 20 (0.15 mg), proline (36 mg), and Water for Injection, USP at pH 4.8.
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.
Animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of SILIQ. The published literature is mixed on the potential effects on malignancy risk due to the inhibition of the IL-17RA, the pharmacological action of SILIQ. Some published literature suggests that IL-17A directly promotes cancer cell invasion, which suggests a potential beneficial effect of SILIQ. However, other reports indicate IL-17A promotes T-cell mediated tumor rejection, which suggests a potential adverse effect by SILIQ. However, inhibition of the IL-17RA with SILIQ has not been studied in these models. Therefore, the relevance of experimental findings in these models for malignancy risk in humans is unknown.
In cynomolgus monkeys, there were no effects on fertility parameters such as changes in reproductive organs or sperm analysis following subcutaneous administration of brodalumab at dose levels up to 90 mg/kg/week for 6 months (26 times the MRHD on a mg/kg basis). The monkeys were not mated in this study to evaluate effects on fertility.
Three multicenter, randomized, double-blind, controlled trials (Trials 1, 2, and 3) enrolled a total of 4373 subjects 18 years of age and older with at least a 6-month history of moderate to severe plaque psoriasis, defined as having a minimum affected body surface area (BSA) of 10%, a Psoriasis Area and Severity Index (PASI) score ≥ 12, a static Physician’s Global Assessment (sPGA) score ≥3 in the overall assessment (plaque thickness/induration, erythema, and scaling) of psoriasis on a severity scale of 0 to 5, and 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.
Other evaluated outcomes included the proportion of subjects who achieved an sPGA of 0 (clear) at Week 12, and the proportion of subjects who achieved a Psoriasis Symptom Inventory (PSI) score of 0 (not at all) or 1 (mild) on every item (itch, redness, scaling, burning, stinging, cracking, flaking, and pain) at Week 12. Baseline demographics and disease characteristics were generally consistent across all treatment groups in all three trials. Subjects were predominantly men (69%) and white (91%), with a mean age of 45 years. The mean baseline body weight was 90.5 kg and 28% of subjects had body weight greater than 100 kg. The baseline PASI score ranged from 9.4 to 72 (median: 17.4) and the baseline- affected BSA ranged from 10 to 97% (median: 21%). Baseline sPGA scores ranged from “3 (moderate)” (58%) to “5 (very severe)” (5%).
Approximately 21% of subjects had a history of psoriatic arthritis. Approximately 30% of subjects had previously received a biologic therapy and 12% of subjects had failed previous biologic therapy.
The results of Trials 1, 2, and 3 are presented in
Endpoint | Trial 1 | Trial 2 | Trial 3 | |||||
SILIQ 210 mg Q2W (N=222) n (%) | Placebo (N=220) n (%) | SILIQ 210 mg Q2W (N=612) n (%) | Ustekinumab (N=300) n (%) | Placebo (N=309) n (%) | SILIQ 210 mg Q2W (N=624) n (%) | Ustekinumab (N=313) n (%) | Placebo (N=315) n (%) | |
PASI 75 | 185 (83) | 6 (3) | 528 (86) | 210 (70) | 25 (8) | 531 (85) | 217 (69) | 19 (6) |
PASI 100 response | 93 (42) | 1 (<1) | 272 (44) | 65 (22) | 2 (1) | 229 (37) | 58 (19) | 1 (<1) |
sPGA | 168 (76) | 3 (1) | 481 (79) | 183 (61) | 12 (4) | 497 (80) | 179 (57) | 13 (4) |
sPGA of clear (0) | 93 (42) | 1 (<1) | 274 (45) | 65 (21) | 2 (1) | 229 (37) | 58 (19) | 1 (<1) |
Examination of age, gender, race, use of prior systemic or phototherapy, and use of prior biologics did not identify differences in response to SILIQ among these subgroups.
At Week 12, compared to subjects in the placebo group, a greater proportion of subjects in SILIQ 210 mg Q2W group achieved a Psoriasis Symptom Inventory (PSI) score of 0 (not at all) or 1 (mild) on every item (itch, redness, scaling, burning, stinging, cracking, flaking, pain).
In Trial 1, subjects randomized to receive SILIQ and who were responders at Week 12 (i.e., sPGA of 0 or 1) were re-randomized to receive either placebo or SILIQ. Among responders at Week 12, 83% (69/83) of subjects re-randomized to continued treatment with SILIQ 210 mg Q2W maintained this response (sPGA of 0 or 1) at Week 52 compared to none (0/84) who were re-randomized to placebo and withdrawn from SILIQ. In addition, 87% (72/83) of subjects re-randomized to continued treatment with SILIQ 210 mg Q2W achieved PASI 75 response at Week 52 compared to none (0/84) who were re-randomized to placebo and withdrawn from SILIQ.
Trials 2 and 3 included a re-randomized phase during which subjects originally randomized to receive SILIQ during the first 12 weeks were re-randomized to one of four SILIQ regimens at the Week 12 visit and placebo subjects were crossed over to receive SILIQ 210 mg Q2W. Subjects receiving ustekinumab continued the same treatment until crossed over at Week 52 to SILIQ 210 mg Q2W. For sPGA 0 or 1 responders at Week 12, the percentage of subjects who maintained this response at Week 52 was 79% for subjects treated with SILIQ 210 mg Q2W. For PASI 100 responders at Week 12, 72% of the subjects who continued on SILIQ 210 mg Q2W maintained the response at Week 52.
SILIQ
®(brodalumab) injection is available in a single-dose prefilled syringe containing a sterile, preservative-free clear to slightly opalescent, colorless to slightly yellow solution.
- NDC 0187-0004-02: Carton of two 210 mg/1.5 mL single-dose prefilled syringes
- Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light and physical damage during storage.
- When necessary, prefilled syringes can be stored at room temperature up to a maximum of 77°F (25°C) in the original carton for a maximum single period of 14 days with protection from light and sources of heat. Once the prefilled syringe has reached room temperature, do not place back into the refrigerator. Discard after 14 days at room temperature.
- Do not freeze.
- Do not shake.
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.
