Ixekizumab

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 == Contraindications ==

The medication is contraindicated for patients with certain infections such as active tuberculosis. == 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%). Ixekizumab does not have an increased risk of adverse effects in the elderly. == Overdose ==

Up to fourfold doses have been given in studies without causing serious side effects. == 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. == 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. With the usual dosing scheme (loading plus a dose every two weeks), steady state concentrations are reached in the eighth week on average. The volume of distribution is 7.11 L. == Chemistry ==

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. == History ==

Clinical trials included a Phase II trial of patients with moderate to severe psoriasis, and a Phase III open-label trial. 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 trials were conducted in the US, Canada, Europe, Russia, Mexico, Chile, Argentina, Japan and Australia. == References ==