Ixekizumab

Overview

Ixekizumab, sold under the brand name Taltz, is an injectable medication for the treatment of autoimmune diseases. Chemically, it is a form of a humanized monoclonal antibody. The substance acts by binding interleukin 17A and neutralizing it, reducing inflammation.[1][2][3] WP

The most common side effects include upper respiratory infections, injection site reactions and fungal (tinea) infections.[4] WP

The drug was developed by Eli Lilly and Co. and is approved for the treatment of plaque psoriasis in the European Union and the United States as of 2016.[5][6] WP

Uses, dosage and effects

Medical uses

In the United States, ixekizumab is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy, active psoriatic arthritis, active ankylosing spondylitis, and active non-radiographic axial spondyloarthritis with objective signs of inflammation. In the European Union it is indicated for the treatment of moderate-to-severe plaque psoriasis and as a second-line therapy for active psoriatic arthritis.[2][5][7] WP

In studies, the drug reduced the Psoriasis Area and Severity Index by at least 75% (PASI75) in 82–89% of patients during the first three months of treatment (depending on the dosing scheme), and 40% of patients experienced a complete absence of psoriasis symptoms (PASI100). In the placebo group, PASI75 was reached in 4% of patients, and PASI100 in none; in the group of patients receiving etanercept, an older anti-psoriasis drug, PASI75 was reached in 48%. Until the 60th study week, 11–44% of ixekizumab treated patients relapsed (again, depending on the dosing scheme), as compared to 84% under placebo.[2][8] WP

Risks and side effects

Contraindications

The medication is contraindicated for patients with certain infections such as active tuberculosis.[2] WP⚠ Part of this sentence could not be copied from the source. Open the source to read it in full.

Adverse effects

In studies, ixekizumab increased the rate of infections (27% of ixekizumab treated patients, compared to 23% under placebo), including severe ones (0.6% versus 0.4% under placebo). Other common side effects included injection site reactions such as redness and pain (13–17% versus 3%), oropharyngeal pain (1%) and nausea (1–2%). Other common adverse effects (≥5.0%) include nasopharyngitis, upper respiratory tract infection, arthralgia, headache, back pain, hypertension, bronchitis, diarrhea, sinusitis, and urinary tract infection.[2][9][10] WP

In a review of 18,025 patient years (n=6892 patients), no anaphylaxis was reported, no reactivation of tuberculosis, and low incidence rate of candida infection and serious infections was found. Incidence rates decreased or remained constant over time.[10] WP

Ixekizumab does not have an increased risk of adverse effects in the elderly.[11] WP

Overdose

Up to fourfold doses have been given in studies without causing serious side effects.[2] WP

Interactions

Interactions

No interaction studies have been done. Ixekizumab and interleukin 17 are not known to interact with cytochrome P450 (CYP) liver enzymes. Since inflammation suppresses CYP activity, it is theorized that ixekizumab could neutralize this effect and lower blood plasma concentrations of drugs that are metabolized by CYP enzymes, such as warfarin.[2] WP

Pharmacology

Mechanism of action

Ixekizumab binds to interleukin 17 (IL-17A), a pro-inflammatory cytokine, and blocks its action. Among other things, IL-17A stimulates proliferation and activation of keratinocytes in the skin. This mechanism is similar to that of another anti-psoriasis antibody, brodalumab, which binds to the interleukin-17 receptor.[2][12] WP

The antibody has affinity to the homodimer IL-17A and the heterodimer IL-17A/F, but not to other members of the interleukin 17 family.[2] WP

Pharmacokinetics

After subcutaneous injection, ixekizumab has a bioavailability of 60–81%; bioavailability is higher in the thigh than the abdomen or arm. Highest blood plasma concentrations are reached after four to seven days after a single dose. With the usual dosing scheme (loading plus a dose every two weeks), steady state concentrations are reached in the eighth week on average.[2][13][14] WP

Like other antibodies, ixekizumab is probably degraded by proteolysis. Its elimination half-life is 14–18 days. The volume of distribution is 7.11 L. Mean clearance is 0.39 L/day. There is no difference in rate of clearance between elderly and younger patients. Increased body weight increases the volume of distribution and clearance rate. Ixekizumab displays linear pharmacokinetics across doses.[2][11][14][15] WP

Pharmacokinetic data is similar for autoinjector pens and prefilled syringes.[13] WP

History

History

Clinical trials included a Phase II trial of patients with moderate to severe psoriasis, and a Phase III open-label trial.[12][16] WP

Ixekizumab was approved by the US Food and Drug Administration (FDA) in March 2016, for the treatment of adults with moderate-to-severe plaque psoriasis and by the European Medicines Agency (EMA) in April 2016. The safety and efficacy of ixekizumab were established in three randomized, placebo-controlled clinical trials with a total of 3,866 participants with plaque psoriasis who were candidates for systemic or phototherapy therapy. The FDA approved ixekizumab based on the evidence from three clinical trials of 1958 participants with moderate to severe psoriasis. The trials were conducted in the US, Canada, Europe, Russia, Mexico, Chile, Argentina, Japan and Australia.[4][5][17] WP

In December 2017, the FDA approved it for active psoriatic arthritis.[18] WP

Chemistry

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Statement On A Nonproprietary Name Adopted By The USAN Council: Ixekizumab
2. Other Austria-Codex. 2015
3. Journal / agency Cai Y, Fleming C, Yan J. Dermal γδ T cells--a new player in the pathogenesis of psoriasis. International Immunopharmacology. July 2013. doi:10.1016/j.intimp.2013.02.018 · PMID 23499509
4. Journal / agency FDA approves new psoriasis drug Taltz. 22 March 2016
5. Journal / agency Taltz EPAR. 2 May 2016
6. Journal / agency Taltz (ixekizumab) Injection. 3 May 2016
7. Journal / agency Taltz- ixekizumab injection, solution. 23 August 2019
8. Journal / agency Klement A. Taltz. Österreichische Apothekerzeitung. 4 June 2016
9. Journal / agency Shear NH, Paul C, Blauvelt A, Gooderham M, Leonardi C, Reich K, Ohtsuki M, Pangallo B, Xu W, Ball S, Ridenour T, Torisu-Itakura H, Agada N, Mallbris L. Safety and Tolerability of Ixekizumab: Integrated Analysis of Injection-Site Reactions from 11 Clinical Trials. Journal of Drugs in Dermatology. February 2018. PMID 29462229
10. Journal / agency Griffiths CE, Gooderham M, Colombel JF, Terui T, Accioly AP, Gallo G, Zhu D, Blauvelt A. Safety of Ixekizumab in Adult Patients with Moderate-to-Severe Psoriasis: Data from 17 Clinical Trials with Over 18,000 Patient-Years of Exposure. Dermatology and Therapy. June 2022. doi:10.1007/s13555-022-00743-9 · PMID 35624407 · PMC9209552
11. Journal / agency Di Lernia V, Goldust M. An overview of the efficacy and safety of systemic treatments for psoriasis in the elderly. Expert Opinion on Biological Therapy. August 2018. doi:10.1080/14712598.2018.1504016 · PMID 30032682
12. Journal / agency Neue Antikörper in der Pipeline. Pharmazeutische Zeitung. 2012
13. Journal / agency Vu TT, Gooderham M, Papp K. Ixekizumab for treatment of adults with moderate-to-severe plaque psoriasis and psoriatic arthritis. Expert Review of Clinical Pharmacology. November 2016. doi:10.1080/17512433.2016.1242409 · PMID 27690669
14. Journal / agency Kiwalkar S, Beier S, Deodhar A. Ixekizumab for treating ankylosing spondylitis. Immunotherapy. October 2019. doi:10.2217/imt-2019-0094 · PMID 31530049
15. Journal / agency Dyring-Andersen B, Skov L, Zachariae C. Ixekizumab for treatment of psoriasis. Expert Review of Clinical Immunology. April 2015. doi:10.1586/1744666X.2015.1023295 · PMID 25748485
16. Other ClinicalTrialsGov NCT01624233 A Study in Japanese Participants With Moderate-to-Severe Psoriasis
17. Journal / agency Drug Trials Snapshots: Taltz. 22 March 2016
18. Other FDA approves Taltz for psoriatic arthritis in adults. 4 December 2017

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