If you wish to report an adverse event or product complaint, please call 1-800-LILLYRX (1-800-545-5979)
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling.
What is the mechanism of action of mirikizumab in inflammatory bowel disease?
Mirikizumab is a humanized monoclonal antibody directed against interleukin-23, a key cytokine in the inflammatory process of IBD.
Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn's disease (CD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract.1-3
Although the immune response to commensal microbiota is usually self-limiting, in patients with UC or CD, environmental factors and genetic susceptibility can combine with overactivation of the immune response to cause impaired barrier function of the intestinal wall.1-3
This exaggerated immune response causes the release of proinflammatory cytokines leading to additional inflammation.2
The exacerbated inflammatory response leads to
- epithelial breakdown
- depleted goblet cells
- an impaired mucus layer in UC, or
- intestinal wall fibrosis in CD.2-4
Role of Interleukin-23 in Inflammatory Bowel Disease
Interleukin-23 (IL-23), released from activated dendritic cells and macrophages, is a key cytokine in the inflammatory processes of IBD, facilitating the release of
- tumor necrosis factor alpha (TNF-alpha)
- interleukin-21 (IL-21), and
- interleukin-17 (IL-17).1
Mechanism of Action
Mirikizumab is a humanized immunoglobulin G4-variant monoclonal antibody directed against the p19 subunit of human IL-23. Mirikizumab neutralizes IL-23, preventing it from activating the IL-23 receptor complex ().5-8
Mirikizumab does not bind to the p40 subunit, which is shared between IL-23 and interleukin-12 (IL-12), and thus mirikizumab has no effect on IL-12. The mirikizumab/IL-23 complex does not interfere with IL-12 signaling ().5-8
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Abraham C, Cho JH. IL-23 and autoimmunity: new insights into the pathogenesis of inflammatory bowel disease. Annu Rev Med. 2009;60:97-110. https://doi.org/10.1146/annurev.med.60.051407.123757
2Neurath MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol. 2014;14(5):329-342. https://doi.org/10.1038/nri3661
3Ungaro R, Mehandru S, Allen PB, et al. Ulcerative colitis. Lancet. 2017;389(10080):1756-1770. https://doi.org/10.1016/S0140-6736(16)32126-2
4Rieder F, Brenmoehl J, Leeb S, et al. Wound healing and fibrosis in intestinal disease. Gut. 2007;56(1):130-139. https://doi.org/10.1136/gut.2006.090456
5Maari C, Bissonnette R, Papp KA, et al. Safety, efficacy, and pharmacokinetics of a p19-directed IL-23 antibody in patients with plaque psoriasis and healthy subjects. Poster presented at: 25th Congress of the European Academy of Dermatology and Venereology; September 28-October 2, 2016; Vienna, Austria.
6Baker KF, Isaacs JD. Novel therapies for immune-mediated inflammatory diseases: what can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn's disease and ulcerative colitis? Ann Rheum Dis. 2018;77(2):175-187. https://doi.org/10.1136/annrheumdis-2017-211555
7Reich K, Rich P, Maari C, et al. Efficacy and safety of mirikizumab (LY3074828) in the treatment of moderate-to-severe plaque psoriasis: results from a randomized phase II study. Br J Dermatol. 2019;181(1):88-95. https://doi.org/10.1111/bjd.17628
8Sandborn WJ, Ferrante M, Bhandari BR, et al. Efficacy and safety of mirikizumab in a randomized phase 2 study of patients with ulcerative colitis. Gastroenterology. 2020;158(3):537-549.e10. https://doi.org/10.1053/j.gastro.2019.08.043
9Hamza T, Barnett JB, Li B. Interleukin 12 a key immunoregulatory cytokine in infection applications. Int J Mol Sci. 2010;11(3):789-806. https://doi.org/10.3390/ijms11030789
10Tugues S, Burkhard SH, Ohs I, et al. New insights into IL-12-mediated tumor suppression. Cell Death Differ. 2015;22(2):237-246. https://doi.org/10.1038/cdd.2014.134
11Teng MWL, Bowman EP, McElwee JJ, et al. IL-12 and IL-23 cytokines: from discovery to targeted therapies for immune-mediated inflammatory diseases. Nat Med. 2015;21(7):719-729. https://doi.org/10.1038/nm.3895
Date of Last Review: January 21, 2021