Medical Editor: John P. Cunha, DO, FACOEP
Siliq (brodalumab) injection is a human interleukin-17 receptor A (IL-17RA) antagonist 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. Common side effects of Siliq include:
- joint pain,
- mouth and throat pain,
- muscle pain,
- injection site reactions (pain, redness, bruising, bleeding, itching),
- low white blood cell count (neutropenia), and
- tinea infections (such as ringworm, athlete's foot, jock itch).
Suicidal thoughts or behavior, or worsening depression may occur while taking Siliq, especially in patients with a history of depression and suicidal thoughts or behavior. Tell your doctor if this occurs.
The recommended Siliq dose is 210 mg administered by subcutaneous injection at Weeks 0, 1, and 2 followed by 210 mg every 2 weeks. Siliq is available only through a restricted program called the Siliq REMS Program because of the observed suicidal ideation and behavior in subjects treated with Siliq. Siliq may interact with “live” vaccines, warfarin, and cyclosporine. Tell your doctor all medications and supplements you use and all vaccines you recently received. Tell your doctor if you are pregnant or plan to become pregnant before using Siliq; it is unknown how it will affect a fetus. It is unknown if Siliq passes into breast milk or if it might affect a nursing infant. Consult your doctor before breastfeeding.
Our Siliq (brodalumab) Injection Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
The following serious adverse reactions are discussed in greater detail in other sections of labeling:
- Suicidal Ideation and Behavior [see WARNINGS AND PRECAUTIONS]
- Infections [see WARNINGS AND PRECAUTIONS]
- Crohn's Disease [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS]
Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The overall safety population included 4558 subjects (3066 SILIQ, 613 ustekinumab, 879 placebo) in controlled clinical trials and open-label extension studies. The majority of subjects were male (69%), white (91%), and aged 40-64 years old Â (58%). One-third of subjects reported previous biologic use prior to enrollment. Across the clinical development program, 4464 subjects received at least one dose of SILIQ; 3755 subjects were exposed to SILIQ for at least 1 year.
Weeks 0 to 12: Data from one multicenter, randomized, placebo-controlled trial (Trial 1), two multicenter, randomized, placebo-and active-controlled trials (Trials 2 and 3), and one dose-finding trial (Trial 4) in plaque psoriasis were pooled to evaluate the safety of SILIQ (210 mg weekly at Weeks 0, 1, and 2, followed by treatments every 2 weeks [Q2W]) compared to placebo for up to 12 weeks after treatment initiation.
During the 12-week, randomized treatment period, about 1% of the subjects in the treatment groups (SILIQ, ustekinumab and placebo) discontinued treatment because of adverse events. Adverse events leading to discontinuation of SILIQ included neutropenia, arthralgia, and urticaria. The proportion of subjects who developed serious adverse events was similar among the SILIQ, ustekinumab, and placebo groups.
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the SILIQ 210 mg Q2W group than in the placebo group during the 12-week randomized treatment period of the pooled trials.
Table 1: Adverse Reactions Occurring in ≥ 1% of
Subjects in the SILIQ Group and More Frequently than in the Placebo Group in Plaque
Psoriasis Trials through Week 12
|SILIQ 210 mg every 2 weeksa
|Arthralgia||29 (3.3)||71 (4.7)||15 (2.4)|
|Headache||31 (3.5)||64 (4.3)||23 (3.8)|
|Fatigue||10 (1.1)||39 (2.6)||16 (2.6)|
|Diarrhea||10 (1.1)||33 (2.2)||5 (0.8)|
|Oropharyngeal pain||10 (1.1)||31 (2.1)||8 (1.3)|
|Nausea||10 (1.1)||28 (1.9)||6 (1.0)|
|Myalgia||3 (0.3)||26 (1.7)||4 (0.7)|
|Injection site reactions (pain, erythema, bruising, hemorrhage, pruritus)||11 (1.3)||23 (1.5)||12 (2.0)|
|Influenza||4 (0.5)||19 (1.3)||7 (1.1)|
|Neutropenia||4 (0.5)||15 (1.0)||5 (0.8)|
|Tinea infections (tinea pedis, versicolor, cruris)||2 (0.2)||15 (1.0)||3 (0.5)|
|a subjects receiving 210 mg of SILIQ at Weeks
0, 1, and 2, followed by treatment every two weeks during the 12-week period
b Trials 2 and 3 included the active comparator, ustekinumab.
Adverse reactions that occurred in less than 1% of subjects in the SILIQ group through Week 12 were conjunctivitis and candida infections (including oral [0.2%], genital [0.1%], and esophageal [0.1%] versus none in the placebo group).
Week 0 to End of Trial: Through Week 52, exposure-adjusted rates of serious adverse events were similar between subjects treated with SILIQ and those treated with ustekinumab. Through the end of the trial, the exposure-adjusted rates of treatment-emergent serious adverse events were similar to those seen in the 52-week period in the subjects treated with SILIQ.
Specific Adverse Reactions
Suicidal Ideation and Behavior
During the 12-week randomized treatment period in the pooled trials, one subject in the SILIQ group attempted suicide and none in the placebo or ustekinumab groups. From initiation through Week 52 of the trials, suicidal ideation or behavior occurred in 7 of 4019 subjects (0.2 per 100 subject-years) treated with SILIQ and in 2 of 613 subjects (0.4 per 100 subject-years) treated with ustekinumab.
During the course of the clinical trials for plaque psoriasis, suicidal ideation or behavior occurred in 34 of 4464 subjects treated with SILIQ (0.37 per 100 subject-years). Eight of the 10 subjects who attempted or completed suicide had a history of depression and/or suicidal ideation or behavior [see WARNINGS AND PRECAUTIONS].
During the 12-week randomized treatment period, infections occurred in 25.4% of the SILIQ group compared to 23.4% of the placebo group. The majority of infections consisted of nasopharyngitis, upper respiratory tract infection, pharyngitis, urinary tract infections, bronchitis, and influenza, and did not necessitate treatment discontinuation. The SILIQ group had a higher rate of fungal infections compared to the placebo group (1.8% vs 0.9%). The fungal infections were primarily non-serious skin and mucosal candida infections [see WARNINGS AND PRECAUTIONS].
During the 12-week randomized treatment period, neutropenia occurred in 0.7% of subjects in the SILIQ group. Most adverse reactions of neutropenia were transient. In subjects with normal absolute neutrophil count (ANC) at baseline, a reduction in ANC occurred in 6.8% of subjects in the SILIQ group, compared to 3.3% in the ustekinumab group, and 3.6% in the placebo group. Neutropenia ≥ Grade 3 ( < 1000/mm²) occurred in 0.5% of subjects in the SILIQ group compared to 0.2% of subjects in the ustekinumab group and none in the placebo group. From Week 0 to end of trial, the exposure-adjusted rate of treatment-emergent neutropenia was 0.4 per 100 subject-years (0.1 per 100 subject-years were ≥ Grade 3). No serious infections were associated with cases of neutropenia.
As with all therapeutic proteins, there is potential for immunogenicity with SILIQ. Approximately 3% of subjects treated with SILIQ developed antibodies to brodalumab through the 52-week treatment period. Of the subjects who developed antibodies to brodalumab, none had antibodies that were classified as neutralizing. However, the assay to test for neutralizing antibodies had limitations detecting neutralizing antibodies in the presence of brodalumab; therefore, the incidence of neutralizing antibody development could be underestimated.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to SILIQ with the incidence of antibodies to other products may be misleading.
Read the entire FDA prescribing information for Siliq (Brodalumab Injection for Subcutaneous Use)