What is Taltz (ixekizumab)?

Taltz (ixekizumab) is a type of injectable biologic drug called a humanized interleukin-17A antagonist used to treat moderate to severe plaque psoriasis in patients who are candidates for phototherapy or medications that are absorbed into the bloodstream (systemic therapy). 

Scientists believe psoriasis is caused by an increase in the production of T-lymphocytes in response to the attachment of a stimulant, such as interleukin, to the lymphocyte. Stimulated T-lymphocytes cause skin cells to grow rapidly, and the rapid growth of the skin cells produces the skin plaques of psoriasis

Taltz reduces symptoms of psoriasis (inflammation and excessive production of skin cells) by attaching to IL-17A, preventing it from binding and activating T-lymphocytes.

Common side effects of Taltz include:

Serious side effects of Taltz include:

Drug interactions of Taltz include live vaccines because patients may develop active disease from the live viruses contained in the vaccine due to their weakened immune system. Taltz may indirectly alter blood levels of warfarin, cyclosporine, and other drugs metabolized by liver enzymes called CYP450 because the formation of these liver enzymes is affected by the level of interleukins. 

Use of Taltz in pregnant women has not been adequately evaluated. It is unknown if Taltz is secreted in breast milk or if there are effects on the nursing infant. Consult your doctor before breastfeeding.

What are the important side effects of Taltz (ixekizumab)?

Common side effects include:

Other important side effects include:

Possible serious side effects include:

Ixekizumab increases the risk of infections. Therefore, patients should be evaluated for a history of latent or active tuberculosis infections. Patients with active tuberculosis infection should not receive Ixekizumab.

Taltz (ixekizumab) side effects list for healthcare professionals

The following adverse drug reactions are discussed in greater detail in other sections of the label:

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.

Plaque Psoriasis

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 2 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.

Table 1: Adverse Reactions Occurring in ≥1% of the Taltz Group and More Frequently than in the Placebo Group in the Plaque Psoriasis Clinical Trials through Week 12

Adverse ReactionsTaltz 80 mg Q2W
(N=1167) n (%)
Etanerceptb
(N=287) n(%)
Placebo
(N=791) n(%)
Injection site reactions196 (17)32 (11)26 (3)
Upper respiratory tract infectionsa163 (14)23 (8)101 (13)
Nausea23 (2)1 (<1)5 (1)
Tinea infections17 (2)01 (<1)
a Upper respiratory tract infections cluster includes nasopharyngitis and rhinovirus infection.
b U.S. approved etanercept.

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 followup), 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-tomoderate 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/mm²) 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/mm²) or Grade 1 (7% for Taltz 80 mg Q2W versus 3% for placebo; ≥1,500 cells/mm² to <2,000 cells/mm²). 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/mm² to <150,000 cells/mm²). 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.

Psoriatic Arthritis

Taltz was studied in two placebo-controlled trials in patients with psoriatic arthritis. A total of 678 patients were studied (454 patients on Taltz and 224 on placebo). A total of 229 patients in these trials received Taltz 160 mg at Week 0, followed by 80 mg every 4 weeks (Q4W). Overall, the safety profile observed in patients with psoriatic arthritis treated with Taltz Q4W is consistent with the safety profile in patients with plaque psoriasis with the exception of the frequencies of influenza (1.3%) and conjunctivitis (1.3%).

Ankylosing Spondylitis

Taltz was studied in two placebo-controlled trials in patients with ankylosing spondylitis. A total of 566 patients were studied (376 patients on Taltz and 190 on placebo). A total of 195 patients in these trials received Taltz 80 or 160 mg at Week 0, followed by 80 mg every 4 weeks (Q4W). Overall, the safety profile observed in patients with ankylosing spondylitis treated with Taltz Q4W is consistent with the safety profile in patients with plaque psoriasis.

Immunogenicity

As with all therapeutic proteins there is the potential for immunogenicity with Taltz. 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.

Plaque Psoriasis Population

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.

Psoriatic Arthritis Population

For subjects treated with Taltz 80 mg every 4 weeks for up to 52 weeks (PsA1), 11% developed anti-drug antibodies, and 8% had confirmed neutralizing antibodies.

Ankylosing Spondylitis Population

For patients treated with Taltz 80 mg every 4 weeks for up to 16 weeks (AS1, AS2), 5.2% developed anti-drug antibodies, and 1.5% had neutralizing antibodies.

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 across indications or with the incidences of antibodies to other products may be misleading.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Taltz. Because the reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to Taltz exposure.

Immune system disorders: anaphylaxis.

What drugs interact with Taltz (ixekizumab)?

Live Vaccinations

Avoid use of live vaccines in patients treated with Taltz.

Cytochrome P450 Substrates

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. Thus, Taltz, an antagonist of IL-17A, could normalize the formation of CYP450 enzymes.

Therefore, upon initiation or discontinuation of Taltz 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.

Summary

Taltz (ixekizumab) is a type of injectable biologic drug called a humanized interleukin-17A antagonist used to treat moderate to severe plaque psoriasis in patients who are candidates for phototherapy or medications that are absorbed into the bloodstream (systemic therapy). Scientists believe psoriasis is caused by an increase in the production of T-lymphocytes in response to the attachment of a stimulant, such as interleukin, to the lymphocyte. Stimulated T-lymphocytes cause skin cells to grow rapidly, and the rapid growth of the skin cells produces the skin plaques of psoriasis. Common side effects of Taltz include injection site reactions, upper respiratory tract infections, nausea, tinea infections (such as ringworm, athlete's foot and jock itch), runny or stuffy nose, oral thrush, hives, influenza, and conjunctivitis. Use of Taltz in pregnant women has not been adequately evaluated. It is unknown if Taltz is secreted in breast milk or if there are effects on the nursing infant. Consult your doctor before breastfeeding.

Treatment & Diagnosis

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Medically Reviewed on 3/16/2020
References
FDA Prescribing Information
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