Taltz ® (ixekizumab) injection

80 mg/mL

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TALTZ® (ixekizumab): Mechanism of Action in axSpA

Information on the mechanism of action of ixekizumab in axSpA is available in this response.

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TALTZ® (ixekizumab): Mechanism of Action in Axial Spondyloarthritis

Role of Interleukin-17A

IL-17A is a pleiotropic cytokine that is involved in inflammatory functions and host protection against specific pathogens, and is important in inducing specific chemokines (eg, IL-8, CCL20) that recruit leukocytes such as neutrophils. Several cell types have been shown to produce IL-17, including, but not limited to

  • T cells
  • innate lymphoid cells
  • granulocytes, and
  • macrophages.1-3

IL-17A is an important cytokine involved in the immunopathology of axSpA, including

  • inflammation 
  • bone erosion
  • dysregulated bone formation
  • enthesitis, and
  • synovitis.4

Ixekizumab Impact on IL-17A

Ixekizumab is a humanized IgG4 monoclonal antibody that selectively binds with the IL-17A cytokine and inhibits its interaction with its receptor. Disruption of IL-17 binding to its receptor inhibits the release of pro-inflammatory effectors, including cytokines and chemokines which in turn can result in a reduction or inhibition of the inflammatory pathogenic mechanisms described above.1-3

Ixekizumab selectively binds to IL-17A. Ixekizumab was engineered to have an amino acid point mutation in the hinge region to prevent the formation of half antibodies, and thus reduce antibody heterogeneity.5

References

The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).

1Mease P, Lubberts E, McInnes I, van der Heijde D. IL-17 inhibition in spondyloarthritis: a targeted approach in psoriatic arthritis. EMJ Rheumatol. 2015;2(1):55-64. https://www.emjreviews.com/rheumatology/symposium/il-17-inhibition-in-spondyloarthritis-a-targeted-approach-in-psoriatic-arthritis

2Mease PJ, van der Heijde D, Ritchlin CT, et al; SPIRIT-P1 Study Group. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis. 2017;76(1):79-87. http://dx.doi.org/10.1136/annrheumdis-2016-209709

3Nash P, Kirkham B, Okada M, et al; SPIRIT-P2 Study Group. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. Lancet. 2017;389(10086):2317-2327. http://dx.doi.org/10.1016/S0140-6736(17)31429-0

4Raychaudhuri SK, Saxena A, Raychaudhuri SP. Role of IL-17 in the pathogenesis of psoriatic arthritis and axial spondyloarthritis. Clin Rheumatol. 2015;34(6):1019-1023. http://dx.doi.org/10.1007/s10067-015-2961-7

5Liu L, Lu J, Allan BW, et al. Generation and characterization of ixekizumab, a humanized monoclonal antibody that neutralizes interleukin-17A. J Inflamm Res. 2016;9:39-50. http://dx.doi.org/10.2147/JIR.S100940

Glossary

axSpA = axial spondyloarthritis

CCL20 = C-C motif chemokine ligand 20

IgG4 = immunoglobulin G subclass 4

IL = interleukin

Date of Last Review: February 19, 2020


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