|Target||Interleukin 17A (IL-17A)|
|Main uses||Plaque psoriasis, psoriatic arthritis, ankylosing spondylitis|
|Side effects||Respiratory infections, injection site pain|
|Elimination half-life||13 days|
|Chemical and physical data|
|Molar mass||146192.34 g·mol−1|
|(what is this?)|
Ixekizumab, sold under the brand name Taltz, is a medication used to treat plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. For plaque psoriasis it is used for moderate to severe disease. It is given as an injection under the skin.
Common side effects include respiratory infections and injection site pain. Other side effects may include infections and allergic reactions. Safety in pregnancy is unclear. It is a monoclonal antibody that attaches to and blocks interleukin 17A, reducing inflammation.
Ixekizumab was approved for medical use in the Europe and the United States in 2016. In the United Kingdom it costs the NHS about £1,130 per 80 mg dose as of 2021. In the United States this amount costs about 6,250 USD.
Ixekizumab is used to treat 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. It is also used for moderate-to-severe plaque psoriasis.
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.
It is given as an initial dose of 160 mg and than given at a dose of 80 every two to four weeks.
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 pain (13–17% versus 3%), oropharyngeal pain (1%) and nausea (1–2%).
Up to fourfold doses have been given in studies without causing serious side effects.
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.
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.
After subcutaneous injection, ixekizumab has a bioavailability of 54–90%. 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.
Ixekizumab is a complete monoclonal antibody of the subclass IgG4, consisting of two light chains and two heavy chains linked by disulfide bridges. Both heavy chains are glycosylated at the asparagine in position 296. In the hinge region, a serine is replaced by a proline to reduce formation of half-antibodies and heterodimers in the manufacturing process. The terminal lysine found in wild-type IgG4 is removed. The antibody is produced in Chinese hamster ovary cells.
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 USA, Canada, Europe, Russia, Mexico, Chile, Argentina, Japan and Australia.
In December 2017, the FDA approved it for active psoriatic arthritis.
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