Ixekizumab
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];
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Overview
Ixekizumab is a humanized anti-interleukin-17 monoclonal antibody that is FDA approved for the treatment of of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.. Common adverse reactions include injection site reactions, upper respiratory tract infections, nausea, and tinea infections (≥1%)..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
- Administer by subcutaneous injection.
- Recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Ixekizumab in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Ixekizumab in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Ixekizumab FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Ixekizumab in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Ixekizumab in pediatric patients.
Contraindications
Ixekizumab is contraindicated in patients with a previous serious hypersensitivity reaction, such as anaphylaxis, to ixekizumab or to any of the excipients
Warnings
- Infections
- TALTZ may increase the risk of infection. In clinical trials, the TALTZ group had a higher rate of infections than the placebo group (27% vs. 23%). Upper respiratory tract infections, oral candidiasis, conjunctivitis and tinea infections occurred more frequently in the TALTZ group than in the placebo group [see Adverse Reactions (6.1)].
Instruct patients treated with TALTZ to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue TALTZ until the infection resolves.
- Pre-treatment Evaluation for Tuberculosis
- Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with TALTZ. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering TALTZ. Consider anti-TB therapy prior to initiating TALTZ in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving TALTZ should be monitored closely for signs and symptoms of active TB during and after treatment.
- Hypersensitivity
- Serious hypersensitivity reactions, including angioedema and urticaria (each ≤0.1%), occurred in the TALTZ group in clinical trials. If a serious hypersensitivity reaction occurs, discontinue TALTZ immediately and initiate appropriate therapy [see Adverse Reactions (6.1)].
- Inflammatory Bowel Disease
- Crohn's disease and ulcerative colitis, including exacerbations, occurred at a greater frequency in the TALTZ group (Crohn's disease 0.1%, ulcerative colitis 0.2%) than the placebo group (0%) during the 12-week, placebo-controlled period. During TALTZ treatment, monitor for onset or exacerbation of inflammatory bowel disease.
- Immunizations
- Prior to initiating therapy with TALTZ, consider completion of all age appropriate immunizations according to current immunization guidelines. Avoid use of live vaccines in patients treated with TALTZ. No data are available on the response to live or inactive vaccines.
Adverse Reactions
Clinical Trials Experience
The following adverse drug reactions are discussed in greater detail in other sections of the label:
- Infections
- Hypersensitivity Reactions
- Inflammatory Bowel Disease
Clinical Trials Experience
Because clinical trials are conducted under widely varying and controlled 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.
Weeks 0 to 12:
Three placebo-controlled trials in subjects with plaque psoriasis were integrated to evaluate the safety of TALTZ compared to placebo for up to 12 weeks. A total of 1167 subjects (mean age 45 years; 66% men; 94% White) with plaque psoriasis received TALTZ (160 mg at Week 0, 80 mg every two weeks [Q2W] for 12 weeks) subcutaneously. In two of the trials, the safety of TALTZ (use up to 12 weeks) was also compared with an active comparator, U.S. approved etanercept.
In the 12-week, placebo-controlled period, adverse events occurred in 58% of the TALTZ Q2W group (2.5 per subject-year of follow-up) compared with 47% of the placebo group (2.1 per subject-year of follow-up). Serious adverse events occurred in 2% of the TALTZ group (0.07 per subject-year of follow-up), and in 2% of the placebo group (0.07 per subject-year of follow-up).
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the TALTZ group than in the placebo group during the 12-week placebo-controlled period of the pooled clinical trials.
Adverse reactions that occurred at rates less than 1% in the TALTZ group and more frequently than in the placebo group during the 12-week induction period included rhinitis, oral candidiasis, urticaria, influenza, conjunctivitis, inflammatory bowel disease, and angioedema.
Weeks 13 to 60:
A total of 332 subjects received the recommended maintenance regimen of TALTZ 80 mg dosed every 4 weeks.
During the maintenance period (Weeks 13 to 60), adverse events occurred in 80% of subjects treated with TALTZ (1.0 per subject-year of follow-up) compared to 58% of subjects treated with placebo (1.1 per subject-year of follow-up). Serious adverse events were reported in 4% of subjects treated with TALTZ (0.05 per subject-year of follow-up) and none in the subjects treated with placebo.
Weeks 0 to 60:
Over the entire treatment period (Weeks 0 to 60), adverse events were reported in 67% of subjects treated with TALTZ (1.4 per subject-year of follow-up) compared to 48% of subjects treated with placebo (2.0 per subject-year of follow-up). Serious adverse events were reported in 3% of subjects treated with TALTZ (0.06 per subject-year of follow-up), and in 2% of subjects treated with placebo (0.06 per subject-year of follow-up).
Specific Adverse Drug Reactions:
Injection Site Reactions
The most frequent injection site reactions were erythema and pain. Most injection site reactions were mild-to-moderate in severity and did not lead to discontinuation of TALTZ.
Infections
In the 12-week, placebo-controlled period of the clinical trials in plaque psoriasis, infections occurred in 27% of subjects treated with TALTZ (1.2 per subject-year of follow-up) compared to 23% of subjects treated with placebo (1.0 per subject-year of follow-up). Serious infections occurred in 0.4% of subjects treated with TALTZ (0.02 per subject-year of follow-up) and in 0.4% of subjects treated with placebo (0.02 per subject-year of follow-up).
During the maintenance treatment period (Weeks 13 to 60), infections occurred in 57% of subjects treated with TALTZ (0.70 per subject-year of follow-up) compared to 32% of subjects treated with placebo (0.61 per subject-year of follow-up). Serious infections occurred in 0.9% of subjects treated with TALTZ (0.01 per subject-year of follow-up) and none in the subjects treated with placebo.
Over the entire treatment period (Weeks 0 to 60), infections were reported in 38% of subjects treated with TALTZ (0.83 per subject-year of follow-up) compared to 23% of subjects treated with placebo (1.0 per subject-year of follow-up). Serious infections occurred in 0.7% of subjects treated with TALTZ (0.02 per subject-year of follow-up), and in 0.4% of subject treated with placebo (0.02 per subject-year of follow-up).
Laboratory Assessment of Cytopenia
Neutropenia
Over the entire treatment period (Weeks 0 to 60), neutropenia occurred in 11% of subjects treated with TALTZ (0.24 per subject-year of follow-up) compared to 3% of subjects treated with placebo (0.14 per subject-year of follow-up). In subjects treated with TALTZ, the incidence rate of neutropenia during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.
In the 12-week, placebo-controlled period, neutropenia ≥ Grade 3 (<1,000 cells/mm3) occurred in 0.2% of the TALTZ group (0.007 per subject-year of follow-up) compared to 0.1% of the placebo group (0.006 per subject-year of follow-up). The majority of cases of neutropenia were either Grade 2 (2% for TALTZ 80 mg Q2W versus 0.3% for placebo; ≥1,000 to <1,500 cells/mm3) or Grade 1 (7% for TALTZ 80 mg Q2W versus 3% for placebo; ≥1,500 cells/mm3 to ˂2,000 cells/mm3). Neutropenia in the TALTZ group was not associated with an increased rate of infection compared to the placebo group.
Thrombocytopenia
Ninety eight percent of cases of thrombocytopenia were Grade 1 (3% for TALTZ 80 mg Q2W versus 1% for placebo; ≥75,000 cells/mm3 to <150,000 cells/mm3). Thrombocytopenia in subjects treated with TALTZ was not associated with an increased rate of bleeding compared to subjects treated with placebo.
Active Comparator Trials
In the two clinical trials that included an active comparator, the rate of serious adverse events during weeks zero to twelve was 0.7% for U.S. approved etanercept and 2% for TALTZ 80 mg Q2W, and the rate of discontinuation from adverse events was 0.7% for U.S. approved etanercept and 2% for TALTZ 80 mg Q2W. The incidence of infections was 18% for U.S. approved etanercept and 26% for TALTZ 80 mg Q2W. The rate of serious infections was 0.3% for both TALTZ 80 mg Q2W and U.S. approved etanercept.
Immunogenicity
As with all therapeutic proteins there is the potential for immunogenicity with TALTZ. By Week 12, approximately 9% of subjects treated with TALTZ every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with TALTZ at the recommended dosing regimen developed antibodies to ixekizumab during the 60-week treatment period. The clinical effects of antibodies to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.
Of the subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with TALTZ at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.
However, the assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies 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 incidence of antibodies to TALTZ with the incidences of antibodies to other products may be misleading.
Postmarketing Experience
There is limited information regarding Ixekizumab Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Ixekizumab Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Ixekizumab in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Ixekizumab in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Ixekizumab during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Ixekizumab in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Ixekizumab in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Ixekizumab in geriatric settings.
Gender
There is no FDA guidance on the use of Ixekizumab with respect to specific gender populations.
Race
There is no FDA guidance on the use of Ixekizumab with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Ixekizumab in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Ixekizumab in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Ixekizumab in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Ixekizumab in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Ixekizumab Administration in the drug label.
Monitoring
There is limited information regarding Ixekizumab Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Ixekizumab and IV administrations.
Overdosage
There is limited information regarding Ixekizumab overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Ixekizumab Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Ixekizumab Mechanism of Action in the drug label.
Structure
There is limited information regarding Ixekizumab Structure in the drug label.
Pharmacodynamics
There is limited information regarding Ixekizumab Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Ixekizumab Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Ixekizumab Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Ixekizumab Clinical Studies in the drug label.
How Supplied
There is limited information regarding Ixekizumab How Supplied in the drug label.
Storage
There is limited information regarding Ixekizumab Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Ixekizumab Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Ixekizumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Ixekizumab Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Ixekizumab Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.