The most common side effects include upper respiratory infections, injection site reactions and fungal (tinea) infections.[12]
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.[6][13]
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.[14] In the European Union it is indicated for the treatment of moderate-to-severe plaque psoriasis[6] and as a second-line therapy for active psoriatic arthritis.[6][10]
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.[10][15]
Contraindications
The medication is contraindicated for patients with certain infections such as active tuberculosis.[10][contradictory]
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.[17]
Ixekizumab does not have an increased risk of adverse effects in the elderly.[18]
Overdose
Up to fourfold doses have been given in studies without causing serious side effects.[10]
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.[10]
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.[10] This mechanism is similar to that of another anti-psoriasis antibody, brodalumab, which binds to the interleukin-17 receptor.[19]
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.[10]
Pharmacokinetics
After subcutaneous injection, ixekizumab has a bioavailability of 60–81%;[7] bioavailability is higher in the thigh than the abdomen or arm.[7] Highest blood plasma concentrations are reached after four to seven days after a single dose.[8] With the usual dosing scheme (loading plus a dose every two weeks), steady state concentrations are reached in the eighth week on average.[10]
Like other antibodies, ixekizumab is probably degraded by proteolysis. Its elimination half-life is 14–18 days.[10][20]
The volume of distribution is 7.11 L.[8] Mean clearance is 0.39 L/day.[8] There is no difference in rate of clearance between elderly and younger patients.[18] Increased body weight increases the volume of distribution and clearance rate.[8] Ixekizumab displays linear pharmacokinetics across doses.[20]
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[12] and by the European Medicines Agency (EMA) in April 2016.[6] 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.[12] The FDA approved ixekizumab based on the evidence from three clinical trials of 1958 participants with moderate to severe psoriasis.[23] The trials were conducted in the US, Canada, Europe, Russia, Mexico, Chile, Argentina, Japan and Australia.[23]
In December 2017, the FDA approved it for active psoriatic arthritis.[24]
^ abcdVu TT, Gooderham M, Papp K (November 2016). "Ixekizumab for treatment of adults with moderate-to-severe plaque psoriasis and psoriatic arthritis". Expert Review of Clinical Pharmacology. 9 (11): 1423–1433. doi:10.1080/17512433.2016.1242409. PMID27690669.
^ abcdeKiwalkar S, Beier S, Deodhar A (October 2019). "Ixekizumab for treating ankylosing spondylitis". Immunotherapy. 11 (15): 1273–1282. doi:10.2217/imt-2019-0094. PMID31530049.
^Cai Y, Fleming C, Yan J (July 2013). "Dermal γδ T cells--a new player in the pathogenesis of psoriasis". International Immunopharmacology. 16 (3): 388–391. doi:10.1016/j.intimp.2013.02.018. PMID23499509.
^Klement A (4 June 2016). "Taltz". Österreichische Apothekerzeitung (in German) (14/2016): 12.
^Shear NH, Paul C, Blauvelt A, Gooderham M, Leonardi C, Reich K, et al. (February 2018). "Safety and Tolerability of Ixekizumab: Integrated Analysis of Injection-Site Reactions from 11 Clinical Trials". Journal of Drugs in Dermatology. 17 (2): 200–206. PMID29462229.
^ abDi Lernia V, Goldust M (August 2018). "An overview of the efficacy and safety of systemic treatments for psoriasis in the elderly". Expert Opinion on Biological Therapy. 18 (8): 897–903. doi:10.1080/14712598.2018.1504016. PMID30032682.
