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Ixekizumab is a humanized IgG4 mAb that selectively binds with the IL-17A cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine involved in normal inflammatory and immune responses. By inhibiting IL-17A, ixekizumab inhibits the release of proinflammatory cytokines and chemokines.1
Ixekizumab does not bind to ligands IL-17B, IL-17C, IL-17D, IL-17E, or IL-17F.2
Elevated levels of IL-17A have been implicated in the pathogenesis of a variety of autoimmune diseases.5
The IL-17A cytokine can be composed of either IL-17A homodimers or IL-17A—IL-17F heterodimers. IL-17A binds to receptor IL-17RA which consists of 2 IL-17RA subunits and 1 IL-17RC subunit.6 IL-17A belongs to a broader family, which includes IL-17A, IL-17B, IL-17C, IL-17D, and IL-17E (Figure 2).
Various cytokines produced by Th17 cells. Th17 cells also produce
Right: Various cell types that produce IL-17A.
Abbreviations: CCL20 = IL-22 and chemokine (C-C motif) ligand 20; GM-CSF = granulocyte macrophage colony-stimulating factor, IL = interleukin; LTi = lymphoid tissue inducer; NK cells = natural killer cells; NKT = natural killer T cells; Th17 = T-helper type 17.
Figure 2. Interleukin-17 Cytokine Family and Receptors9
Enclosed Prescribing Information
2. Tham LS, Tang CC, Choi SL, et al. Population exposure–response model to support dosing evaluation of ixekizumab in patients with chronic plaque psoriasis. J Clin Pharmacol. 2014;54(10):1117-1124. http://dx.doi.org/10.1002/jcph.312
3. Cua DJ, Tato CM. Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol. 2010;10(7): 479-489. http://dx.doi.org/10.1038/nri2800
4. Gaffen SL. Structure and signalling in the IL-17 receptor family. Nat Rev Immunol. 2009;9(8):556-567. http://dx.doi.org/10.1038/nri2586
5. Lin AM, Rubin CJ, Khandpur R, et al. Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis. J Immunol. 2011;187(1):490-500. http://dx.doi.org/10.4049/jimmunol.1100123
6. Chiricozzi A, Krueger JG. IL-17 targeted therapies for psoriasis. Expert Opin Investig Drugs. 2013;22(8):993-1005. http://dx.doi.org/10.1517/13543784.2013.806483
7. Krueger JG, Fretzin S, Suárez-Fariñas M, et al. IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis. J Allergy Clin Immunol. 2012;130(1):145-154.e9. http://dx.doi.org/10.1016/j.jaci.2012.04.024
8. Maddur MS, Miossec P, Kaveri SV, Bayry J. Th17 cells: biology, pathogenesis of autoimmune and inflammatory diseases, and therapeutic strategies. Am J Pathol. 2012;181(1):8-18. http://dx.doi.org/10.1016/j.ajpath.2012.03.044
9. Martin DA, Towne JE, Kricorian G, et al. The emerging role of IL-17 in the pathogenesis of psoriasis: preclinical and clinical findings. J Invest Dermatol. 2013;133(1):17-26. http://dx.doi.org/10.1038/jid.2012.194
IgG4 = immunoglobulin G subclass 4
IL-17 = interleukin-17
mAb(s) = monoclonal antibody
Date of Last Review: August 29, 2018