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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Review Article

Interleukin-23 Blockers: Born to be First-line Biologic Agents in Inflammatory Bowel Disease?

Author(s): Marjorie C. Argollo, Mariangela Allocca, Federica Furfaro, Laurent Peyrin-Biroulet and Silvio Danese*

Volume 25, Issue 1, 2019

Page: [25 - 31] Pages: 7

DOI: 10.2174/1381612825666190313140811

Price: $65

Abstract

Over the past decades, the advent of anti-TNF agents has dramatically changed the treatment algorithms for IBD. However, primarily and more importantly, secondary loss of response to anti-TNF agents, is often observed. Thus, new treatment options have been actively explored and some have already been incorporated in the current clinical practice. Among the class of anti-cytokine agents, the anti-IL12/IL23 monoclonal antibodies (mAbs) have been first presented, in clinical practice, by the anti-p40 mAb ustekinumab in Crohn’s disease (CD). More selective anti-IL23 agents (anti-p19) have shown efficacy and are being further developed, in contrast to agents inhibiting IL-17 downstream, which have failed in IBD clinical trials despite their clear efficacy in psoriasis.

Keywords: Crohn's disease, IL-23, inflammatory bowel disease, monoclonal antibody anti-IL23, Th17 cell pathway cytokines, ulcerative colitis.

« Previous Next »
[1]
Cosnes J, Gower-Rousseau C, Seksik P, Cortot A. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology 2011; 140(6): 1785-94.
[2]
Baumgart DC, Carding SR. Inflammatory bowel disease: Cause and immunobiology. Lancet 2007; 369(9573): 1627-40.
[3]
Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology 2004; 126(6): 1504-17.
[4]
Danese S. Immune and nonimmune components orchestrate the pathogenesis of inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol 2011; 300(5): G716-22.
[5]
Hanauer SB. Inflammatory bowel disease: Epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis 2006; 12(Suppl. 1): S3-9.
[6]
Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature 2011; 474(7351): 307-17.
[7]
Neurath MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol 2014; 14(5): 329-42.
[8]
Roda G, Jharap B, Neeraj N, Colombel J-F. Loss of Response to Anti-TNFs: Definition, Epidemiology, and Management. Clin Transl Gastroenterol 2016; 7(1): e135.
[9]
Ben-Horin S, Chowers Y. Review article: loss of response to anti-TNF treatments in Crohn’s disease. Aliment Pharmacol Ther 2011; 33(9): 987-95.
[10]
Pouillon L, Bossuyt P, Peyrin-Biroulet L. Considerations, challenges and future of anti-TNF therapy in treating inflammatory bowel disease. Expert Opin Biol Ther 2016; 16(10): 1277-90.
[11]
Verstockt B, Ferrante M, Vermeire S, Van Assche G. New treatment options for inflammatory bowel diseases. J Gastroenterol 2018; 53(5): 585-90.
[12]
Lubberts E. The IL-23-IL-17 axis in inflammatory arthritis. Nat Rev Rheumatol 2015; 11(7): 415-29.
[13]
Montalban-Arques A, Chaparro M, Gisbert JP, Bernardo D. The innate immune system in the gastrointestinal tract: Role of intraepithelial lymphocytes and lamina propria innate lymphoid cells in intestinal inflammation. Inflamm Bowel Dis 2018; 24(8): 1649-59.
[14]
Huang Y, Chen Z. Inflammatory bowel disease related innate immunity and adaptive immunity. Am J Transl Res 2016; 8(6): 2490-7.
[15]
Aggarwal S, Ghilardi N, Xie M-H, de Sauvage FJ, Gurney AL. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem 2003; 278(3): 1910-4.
[16]
Gee K, Guzzo C, Che Mat NF, Ma W, Kumar A. The IL-12 family of cytokines in infection, inflammation and autoimmune disorders. Inflamm Allergy Drug Targets 2009; 8(1): 40-52.
[17]
Trinchieri G, Pflanz S, Kastelein RA. The IL-12 family of heterodimeric cytokines: new players in the regulation of T cell responses. Immunity 2003; 19(5): 641-4.
[18]
Parham C, Chirica M, Timans J, et al. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J Immunol 2002; 168(11): 5699-708.
[19]
Duerr RH, Taylor KD, Brant SR, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 2006; 314(5804): 1461-3.
[20]
Iwakura Y, Ishigame H. The IL-23/IL-17 axis in inflammation. J Clin Invest 2006; 116(5): 1218-22.
[21]
Vanden Eijnden S, Goriely S, De Wit D, Willems F, Goldman M. IL-23 up-regulates IL-10 and induces IL-17 synthesis by polyclonally activated naive T cells in human. Eur J Immunol 2005; 35(2): 469-75.
[22]
van de Wetering D, de Paus RA, van Dissel JT, van de Vosse E. IL-23 modulates CD56+/CD3- NK cell and CD56+/CD3+ NK-like T cell function differentially from IL-12. Int Immunol 2009; 21(2): 145-53.
[23]
Ness-Schwickerath KJ, Jin C, Morita CT. Cytokine requirements for the differentiation and expansion of IL-17A- and IL-22-producing human Vgamma2Vdelta2 T cells. J Immunol 2010; 184(12): 7268-80.
[24]
Geremia A, Arancibia-Cárcamo CV, Fleming MPP, et al. IL-23-responsive innate lymphoid cells are increased in inflammatory bowel disease. J Exp Med 2011; 208(6): 1127-33.
[25]
Zhou L, Chong MMW, Littman DR. Plasticity of CD4+ T cell lineage differentiation. Immunity 2009; 30(5): 646-55.
[26]
Bouma G, Strober W. The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol 2003; 3(7): 521-33.
[27]
Hue S, Ahern P, Buonocore S, et al. Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J Exp Med 2006; 203(11): 2473-83.
[28]
Fuss IJ, Becker C, Yang Z, et al. Both IL-12p70 and IL-23 are synthesized during active Crohn’s disease and are down-regulated by treatment with anti-IL-12 p40 monoclonal antibody. Inflamm Bowel Dis 2006; 12(1): 9-15.
[29]
Liu Z, Yadav PK, Xu X, et al. The increased expression of IL-23 in inflammatory bowel disease promotes intraepithelial and lamina propria lymphocyte inflammatory responses and cytotoxicity. J Leukoc Biol 2011; 89(4): 597-606.
[30]
Schmidt C, Giese T, Ludwig B, et al. Expression of interleukin-12-related cytokine transcripts in inflammatory bowel disease: elevated interleukin-23p19 and interleukin-27p28 in Crohn’s disease but not in ulcerative colitis. Inflamm Bowel Dis 2005; 11(1): 16-23.
[31]
Neurath MF, Fuss I, Kelsall BL, Stüber E, Strober W. Antibodies to interleukin 12 abrogate established experimental colitis in mice. J Exp Med 1995; 182(5): 1281-90.
[32]
Tozawa K, Hanai H, Sugimoto K, et al. Evidence for the critical role of interleukin-12 but not interferon-gamma in the pathogenesis of experimental colitis in mice. J Gastroenterol Hepatol 2003; 18(5): 578-87.
[33]
Aujla SJ, Dubin PJ, Kolls JK. Th17 cells and mucosal host defense. Semin Immunol 2007; 19(6): 377-82.
[34]
Hueber W, Sands BE, Lewitzky S, et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut 2012; 61(12): 1693-700.
[35]
Colombel JF, Sendid B, Jouault T, Poulain D. Secukinumab failure in Crohn’s disease: the yeast connection? Gut 2013; 62(5): 800-1.
[36]
Wang K, Karin M. The IL-23 to IL-17 cascade inflammation-related cancers. Clin Exp Rheumatol 2015; 33(4)(Suppl. 92): S87-90.
[37]
Ngiow SF, Teng MWL, Smyth MJ. A balance of interleukin-12 and -23 in cancer. Trends Immunol 2013; 34(11): 548-55.
[38]
Langowski JL, Zhang X, Wu L, et al. IL-23 promotes tumour incidence and growth. Nature 2006; 442(7101): 461-5.
[39]
Błogowski W, Madej-Michniewicz A, Marczuk N, Dołęgowska B, Starzyńska T. Interleukins 17 and 23 in patients with gastric neoplasms. Sci Rep 2016; 6: 37451.
[40]
Punkenburg E, Vogler T, Büttner M, et al. Batf-dependent Th17 cells critically regulate IL-23 driven colitis-associated colon cancer. Gut 2016; 65(7): 1139-50.
[41]
Ryan C, Thrash B, Warren RB, Menter A. The use of ustekinumab in autoimmune disease. Expert Opin Biol Ther 2010; 10(4): 587-604.
[42]
Jr L, Press D. Ustekinumab in treatment of Crohn’s disease: design, development, and potential place in therapy 2016; 3685-98.
[43]
Sandborn WJ, Gasink C, Gao LL, et al. Ustekinumab induction and maintenance therapy in refractory Crohn’s disease. N Engl J Med 2012; 367(16): 1519-28.
[44]
Feagan BG, Sandborn WJ, Gasink C, et al. Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease. N Engl J Med 2016; 375(20): 1946-60.
[45]
Sandborn WJ, Feagan BG, Fedorak RN, et al. A randomized trial of Ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn’s disease. Gastroenterology 2008; 135(4): 1130-41.
[46]
Battat R, Kopylov U, Bessissow T, et al. Association Between Ustekinumab Trough Concentrations and Clinical, Biomarker, and Endoscopic Outcomes in Patients With Crohn’s Disease. Clin Gastroenterol Hepatol 2017; 15(9): 1427-1434.e2.
[47]
Greenup A-J, Rosenfeld G, Bressler B. Ustekinumab use in Crohn’s disease: A Canadian tertiary care centre experience. Scand J Gastroenterol 2017; 52(12): 1354-9.
[48]
Harris KA, Horst S, Gadani A, et al. Patients with Refractory Crohn’s Disease Successfully Treated with Ustekinumab. Inflamm Bowel Dis 2016; 22(2): 397-401.
[49]
Khorrami S, Ginard D, Marín-Jiménez I, et al. Ustekinumab for the Treatment of Refractory Crohn’s Disease: The Spanish Experience in a Large Multicentre Open-label Cohort. Inflamm Bowel Dis 2016; 22(7): 1662-9.
[50]
Kopylov U, Afif W, Cohen A, et al. Subcutaneous ustekinumab for the treatment of anti-TNF resistant Crohn’s disease--the McGill experience. J Crohn’s Colitis 2014; 8(11): 1516-22.
[51]
Ma C, Fedorak RN, Kaplan GG, et al. Clinical, endoscopic and radiographic outcomes with ustekinumab in medically-refractory Crohn’s disease: real world experience from a multicentre cohort. Aliment Pharmacol Ther 2017; 45(9): 1232-43.
[52]
Ma C, Fedorak RN, Kaplan GG, et al. Long-term Maintenance of Clinical, Endoscopic, and Radiographic Response to Ustekinumab in Moderate-to-Severe Crohn’s Disease: Real-world Experience from a Multicenter Cohort Study. Inflamm Bowel Dis 2017; 23(5): 833-9.
[53]
Wils P, Bouhnik Y, Michetti P, et al. Subcutaneous ustekinumab provides clinical benefit for two-thirds of patients with Crohn’s disease refractory to anti-tumor necrosis factor agents. Clin Gastroenterol Hepatol 2016; 14(2): 242-50. e1-2
[54]
Panaccione R, Sandborn WJ, Gordon GL, et al. Briakinumab for treatment of Crohn’s disease: results of a randomized trial. Inflamm Bowel Dis 2015; 21(6): 1329-40.
[55]
Singh S, Kroe-Barrett RR, Canada KA, et al. Selective targeting of the IL23 pathway: Generation and characterization of a novel high-affinity humanized anti-IL23A antibody. MAbs 2015; 7(4): 778-91.
[56]
Argollo M, Fiorino G, Hindryckx P, Peyrin-Biroulet L, Danese S. Novel therapeutic targets for inflammatory bowel disease. J Autoimmun 2017; 85: 103-16.
[57]
Deepak P, Sandborn WJ. Ustekinumab and Anti-Interleukin-23 Agents in Crohn’s Disease. Gastroenterol Clin North Am 2017; 46(3): 603-26.
[58]
Feagan BG, Sandborn WJ, D’Haens G, et al. Induction therapy with the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn’s disease: A randomised, double-blind, placebo-controlled phase 2 study. Lancet 2017; 389(10080): 1699-709.
[59]
Feagan BG, Panes J, Ferrante M, et al. Efficacy and safety of open-label maintenance therapy with subcutaneous risankizumab in patients with moderate-to-severe Crohn’s Disease. Gastroenterology 2017; 152(5): S1310.
[60]
Sands BE, Chen J, Penney M, et al. 830 Initial Evaluation of MEDI2070 (Specific Anti-IL-23 Antibody) in Patients With Active Crohn’s Disease Who Have Failed Anti-TNF Antibody Therapy: A Randomized, Double-Blind Placebo-Controlled Phase 2A Induction Study. Gastroenterology 2015; 148(4): S-163-4.
[61]
Sands BE, Chen J, Feagan BG, et al. Efficacy and safety of MEDI2070, an antibody against interleukin 23, in patients with moderate to severe Crohn’s disease: A phase 2a study. Gastroenterology 2017; 153(1): 77-86.e6.
[62]
Markham A. Guselkumab: First global approval. Drugs 2017; 77(13): 1487-92.
[63]
Zhuang Y, Calderon C, Marciniak SJJ Jr, et al. First-in-human study to assess guselkumab (anti-IL-23 mAb) pharmacokinetics/safety in healthy subjects and patients with moderate-to-severe psoriasis. Eur J Clin Pharmacol 2016; 72(11): 1303-10.
[64]
Sandborn WJ, Ferrante M, Bhandari BR, et al. Efficacy and Safety of Anti-Interleukin-23 Therapy with Mirikizumab (LY3074828) in Patients with Moderate-To-Severe Ulcerative Colitis in a Phase 2 Study. Gastroenterology 2018; 154(6): S-1360-1.
[65]
Papp KA, Griffiths CEM, Gordon K, et al. Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up. Br J Dermatol 2013; 168(4): 844-54.

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