Skip to main content
SpringerLink
Log in

Targeting IL-23 for IBD: Rationale and Progress to Date

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Inflammatory bowel disease, including Crohn’s disease and ulcerative colitis, comprises multiple complex immune-mediated disorders. Early diagnosis and prompt disease control may prevent long-term complications and hospitalization. The therapeutic options have expanded in the last two decades, with the development of biologics and small molecules targeting specific pathways implicated in inflammatory bowel disease pathogenesis. The interleukin (IL)-23/Th-17 axis is one such example. Targeting IL-12/23 is effective for the treatment of both moderate-to-severe Crohn’s disease and ulcerative colitis, and ustekinumab (an IL-12/23p40 antagonist) is approved for both indications. In patients with psoriasis, improved clinical outcomes were observed with agents that more selectively targeted IL-23 (IL-23p19 antagonists) compared with those that target both IL-12 and IL-23. Many specific IL-23p19 antagonists are currently being investigated in Crohn’s disease and ulcerative colitis, and risankizumab has been recently approved for moderate-to-severely active Crohn’s disease. In this review, we summarize the mechanisms of action and the evidence from clinical trials supporting the efficacy and safety of IL-23p19 antagonists for the treatment of inflammatory bowel disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Knowles SR, Graff LA, Wilding H, Hewitt C, Keefer L, Mikocka-Walus A. Quality of life in inflammatory bowel disease: a systematic review and meta-analyses-part I. Inflamm Bowel Dis. 2018;24:742–51.

    Article  PubMed  Google Scholar 

  2. Knowles SR, Keefer L, Wilding H, Hewitt C, Graff LA, Mikocka-Walus A. Quality of life in inflammatory bowel disease: a systematic review and meta-analyses-part II. Inflamm Bowel Dis. 2018;24:966–76.

    Article  PubMed  Google Scholar 

  3. Burisch J, Jess T, Martinato M, Lakatos PL. The burden of inflammatory bowel disease in Europe. J Crohns Colitis. 2013;7:322–37.

    Article  PubMed  Google Scholar 

  4. Kappelman MD, Rifas-Shiman SL, Porter CQ, Ollendorf DA, Sandler RS, Galanko JA, et al. Direct health care costs of Crohn’s disease and ulcerative colitis in US children and adults. Gastroenterology. 2008;135:1907–13.

    Article  PubMed  Google Scholar 

  5. Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W, Benchimol EI, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017;390:2769–78.

    Article  PubMed  Google Scholar 

  6. The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020;5:17–30.

  7. Alsoud D, Verstockt B, Fiocchi C, Vermeire S. Breaking the therapeutic ceiling in drug development in ulcerative colitis. Lancet Gastroenterol Hepatol. 2021;6:589–95.

    Article  PubMed  Google Scholar 

  8. Kayal M, Ungaro RC, Bader G, Colombel JF, Sandborn WJ, Stalgis C. Net remission rates with biologic treatment in Crohn's disease: a reappraisal of the clinical trial data. Clin Gastroenterol Hepatol. 2023;21:1348-1350.

  9. Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359:1541–9.

    Article  CAS  PubMed  Google Scholar 

  10. Gisbert JP, Marín AC, McNicholl AG, Chaparro M. Systematic review with meta-analysis: the efficacy of a second anti-TNF in patients with inflammatory bowel disease whose previous anti-TNF treatment has failed. Aliment Pharmacol Ther. 2015;41:613–23.

    Article  CAS  PubMed  Google Scholar 

  11. Singh S, Murad MH, Fumery M, Sedano R, Jairath V, Panaccione R, et al. Comparative efficacy and safety of biologic therapies for moderate-to-severe Crohn’s disease: a systematic review and network meta-analysis. Lancet Gastroenterol Hepatol. 2021;6:1002–14.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Schmitt H, Billmeier U, Dieterich W, Rath T, Sonnewald S, Reid S, et al. Expansion of IL-23 receptor bearing TNFR2+ T cells is associated with molecular resistance to anti-TNF therapy in Crohn’s disease. Gut. 2019;68:814–28.

    Article  CAS  PubMed  Google Scholar 

  13. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006;314:1461–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Feagan BG, Sandborn WJ, Gasink C, Jacobstein D, Lang Y, Friedman JR, et al. Ustekinumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2016;375:1946–60.

    Article  CAS  PubMed  Google Scholar 

  15. Sands BE, Sandborn WJ, Panaccione R, O’Brien CD, Zhang H, Johanns J, et al. Ustekinumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2019;381:1201–14.

    Article  CAS  PubMed  Google Scholar 

  16. Papp KA, Blauvelt A, Bukhalo M, Gooderham M, Krueger JG, Lacour JP, et al. Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis. N Engl J Med. 2017;376:1551–60.

    Article  CAS  PubMed  Google Scholar 

  17. Feagan BG, Sandborn WJ, D’Haens G, Panés J, Kaser A, Ferrante M, 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;389:1699–709.

    Article  CAS  PubMed  Google Scholar 

  18. Sands BE, Chen J, Feagan BG, Penney M, Rees WA, Danese S, 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;153:77–86.

    Article  CAS  PubMed  Google Scholar 

  19. Sands BE, Peyrin-Biroulet L, Kierkus J, Higgins PDR, Fischer M, Jairath V, et al. Efficacy and safety of mirikizumab in a randomized phase 2 study of patients with Crohn’s disease. Gastroenterology. 2022;162:495–508.

    Article  CAS  PubMed  Google Scholar 

  20. Sandborn WJ, D’Haens GR, Reinisch W, Panés J, Chan D, Gonzalez S, et al. Guselkumab for the treatment of Crohn’s disease: induction results from the phase 2 GALAXI-1 study. Gastroenterology. 2022;162:1650–64.

    Article  CAS  PubMed  Google Scholar 

  21. D'Haens G, Rubin DT, Panes J, Gonzalez S, Chan D, Johanns J, et al. The effect of guselkumab induction therapy on endoscopic outcome measures in patients with moderately to severely active Crohn's disease: week 12 results from the phase 2 GALAXI 1 study. Gastroenteorlogy. 2021;160:S-91.

  22. D’Haens G, Panaccione R, Baert F, Bossuyt P, Colombel JF, Danese S, et al. Risankizumab as induction therapy for Crohn’s disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. Lancet. 2022;399:2015–30.

    Article  CAS  PubMed  Google Scholar 

  23. Ferrante M, Panaccione R, Baert F, Bossuyt P, Colombel JF, Danese S, et al. Risankizumab as maintenance therapy for moderately to severely active Crohn’s disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. Lancet. 2022;399:2031–46.

    Article  CAS  PubMed  Google Scholar 

  24. Sandborn WJ, Ferrante M, Bhandari BR, Berliba E, Feagan BG, Hibi T, et al. Efficacy and safety of mirikizumab in a randomized phase 2 study of patients with ulcerative colitis. Gastroenterology. 2020;158:537–49.

    Article  CAS  PubMed  Google Scholar 

  25. D’Haens G, Kobayashi T, Morris N, Lissoos T, Hoover A, Li X, et al. Efficacy and safety of mirikizumab as induction therapy in patients with moderately to severely active ulcerative colitis: results from the phase 3 LUCENT-1 study. United Eur Gastroenterol J. 2022;10:710–1.

    Google Scholar 

  26. NCT03524092. A maintenance study of mirikizumab in participants with moderately to severely active ulcerative colitis (LUCENT 2). https://clinicaltrials.gov/ct2/show/NCT03524092. Accessed 1 Dec 2022.

  27. Dignass A, Rubin D, Bressler B, Huang KH, Shipitofsky N, Germinaro M, et al. The efficacy and safety of guselkumab induction therapy in patients with moderately to severely active ulcerative colitis: phase 2b QUASAR study results through week 12. J Crohns Colitis. 2022;16:i025-i26.

    Article  Google Scholar 

  28. Sands BE, Feagan BG, Sandborn WJ, Shipitofsky N, Marko M, Sheng S, et al. OP36 efficacy and safety of combination induction therapy with guselkumab and golimumab in participants with moderately-to-severely active ulcerative colitis: results through week 12 of a phase 2a randomized, double-blind, active-controlled, parallel-group, multicenter, proof-of-concept study. J Crohns Colitis. 2022;16:i042-i43.

    Article  Google Scholar 

  29. Kobayashi M, Fitz L, Ryan M, Hewick RM, Clark SC, Chan S, et al. Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J Exp Med. 1989;170:827–45.

    Article  CAS  PubMed  Google Scholar 

  30. Vignali DA, Kuchroo VK. IL-12 family cytokines: immunological playmakers. Nat Immunol. 2012;13:722–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Pirhonen J, Matikainen S, Julkunen I. Regulation of virus-induced IL-12 and IL-23 expression in human macrophages. J Immunol. 2002;169:5673–8.

    Article  CAS  PubMed  Google Scholar 

  32. Cella M, Scheidegger D, Palmer-Lehmann K, Lane P, Lanzavecchia A, Alber G. Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. J Exp Med. 1996;184:747–52.

    Article  CAS  PubMed  Google Scholar 

  33. Macatonia SE, Hosken NA, Litton M, Vieira P, Hsieh CS, Culpepper JA, et al. Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells. J Immunol. 1995;154:5071–9.

    Article  CAS  PubMed  Google Scholar 

  34. Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 2000;13:715–25.

    Article  CAS  PubMed  Google Scholar 

  35. Lupardus PJ, Garcia KC. The structure of interleukin-23 reveals the molecular basis of p40 subunit sharing with interleukin-12. J Mol Biol. 2008;382:931–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Watford WT, Moriguchi M, Morinobu A, O’Shea JJ. The biology of IL-12: coordinating innate and adaptive immune responses. Cytokine Growth Factor Rev. 2003;14:361–8.

    Article  CAS  PubMed  Google Scholar 

  37. Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell. 2000;100:655–69.

    Article  CAS  PubMed  Google Scholar 

  38. Jouanguy E, Döffinger R, Dupuis S, Pallier A, Altare F, Casanova JL. IL-12 and IFN-gamma in host defense against mycobacteria and salmonella in mice and men. Curr Opin Immunol. 1999;11:346–51.

    Article  CAS  PubMed  Google Scholar 

  39. Sun R, Abraham C. IL23 promotes antimicrobial pathways in human macrophages, which are reduced with the IBD-protective IL23R R381Q variant. Cell Mol Gastroenterol Hepatol. 2020;10:673–97.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung 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;168:5699–708.

    Article  CAS  PubMed  Google Scholar 

  41. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006;126:1121–33.

    Article  CAS  PubMed  Google Scholar 

  42. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005;201:233–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Teng MW, Bowman EP, McElwee JJ, Smyth MJ, Casanova JL, Cooper AM, et al. IL-12 and IL-23 cytokines: from discovery to targeted therapies for immune-mediated inflammatory diseases. Nat Med. 2015;21:719–29.

    Article  CAS  PubMed  Google Scholar 

  44. Becker C, Wirtz S, Blessing M, Pirhonen J, Strand D, Bechthold O, et al. Constitutive p40 promoter activation and IL-23 production in the terminal ileum mediated by dendritic cells. J Clin Investig. 2003;112:693–706.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Simmons CP, Goncalves NS, Ghaem-Maghami M, Bajaj-Elliott M, Clare S, Neves B, et al. Impaired resistance and enhanced pathology during infection with a noninvasive, attaching-effacing enteric bacterial pathogen, Citrobacter rodentium, in mice lacking IL-12 or IFN-gamma. J Immunol. 2002;168:1804–12.

    Article  CAS  PubMed  Google Scholar 

  46. Zundler S, Neurath MF. Interleukin-12: functional activities and implications for disease. Cytokine Growth Factor Rev. 2015;26:559–68.

    Article  CAS  PubMed  Google Scholar 

  47. Segal BM, Dwyer BK, Shevach EM. An interleukin (IL)-10/IL-12 immunoregulatory circuit controls susceptibility to autoimmune disease. J Exp Med. 1998;187:537–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. McIntyre KW, Shuster DJ, Gillooly KM, Warrier RR, Connaughton SE, Hall LB, et al. Reduced incidence and severity of collagen-induced arthritis in interleukin-12-deficient mice. Eur J Immunol. 1996;26:2933–8.

    Article  CAS  PubMed  Google Scholar 

  49. Neurath MF, Fuss I, Kelsall BL, Stüber E, Strober W. Antibodies to interleukin 12 abrogate established experimental colitis in mice. J Exp Med. 1995;182:1281–90.

    Article  CAS  PubMed  Google Scholar 

  50. Fuss IJ, Marth T, Neurath MF, Pearlstein GR, Jain A, Strober W. Anti-interleukin 12 treatment regulates apoptosis of Th1 T cells in experimental colitis in mice. Gastroenterology. 1999;117:1078–88.

    Article  CAS  PubMed  Google Scholar 

  51. Yen D, Cheung J, Scheerens H, Poulet F, McClanahan T, McKenzie B, et al. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Investig. 2006;116:1310–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Uhlig HH, McKenzie BS, Hue S, Thompson C, Joyce-Shaikh B, Stepankova R, et al. Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity. 2006;25:309–18.

    Article  CAS  PubMed  Google Scholar 

  53. Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature. 2003;421:744–8.

    Article  CAS  PubMed  Google Scholar 

  54. Karaboga İ, Demirtas S, Karaca T. Investigation of the relationship between the Th17/IL-23 pathway and innate-adaptive immune system in TNBS-induced colitis in rats. Iran J Basic Med Sci. 2017;20:870–9.

    PubMed  PubMed Central  Google Scholar 

  55. Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD, et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet. 2008;40:955–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Maxwell JR, Zhang Y, Brown WA, Smith CL, Byrne FR, Fiorino M, et al. Differential roles for interleukin-23 and interleukin-17 in intestinal immunoregulation. Immunity. 2015;43:739–50.

    Article  CAS  PubMed  Google Scholar 

  57. Hueber W, Sands BE, Lewitzky S, Vandemeulebroecke M, Reinisch W, Higgins PD, 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;61:1693–700.

    Article  CAS  PubMed  Google Scholar 

  58. Targan SR, Feagan B, Vermeire S, Panaccione R, Melmed GY, Landers C, et al. A randomized, double-blind, placebo-controlled phase 2 study of brodalumab in patients with moderate-to-severe Crohn’s disease. Am J Gastroenterol. 2016;111:1599–607.

    Article  CAS  PubMed  Google Scholar 

  59. Aden K, Rehman A, Falk-Paulsen M, Secher T, Kuiper J, Tran F, et al. Epithelial IL-23R signaling licenses protective IL-22 responses in intestinal inflammation. Cell Rep. 2016;16:2208–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Cox JH, Kljavin NM, Ota N, Leonard J, Roose-Girma M, Diehl L, et al. Opposing consequences of IL-23 signaling mediated by innate and adaptive cells in chemically induced colitis in mice. Mucosal Immunol. 2012;5:99–109.

    Article  CAS  PubMed  Google Scholar 

  61. Pai R, De Hertogh G, Reinisch W, Harpaz N, Feagan B, Agada N, et al. Impact of mirikizumab therapy on histologic measures of intestinal inflammation in a phase 2 study of patients with moderately to severely active Crohn’s disease. J Crohns Colitis. 2021;15:S404–6.

    Article  Google Scholar 

  62. Danese S, Panaccione R, Rubin DT, Sands BE, Reinisch W, D’Haens G, et al. Clinical efficacy and safety of guselkumab maintenance therapy in patients with moderately to severely active Crohn’s disease: week 48 analyses from the phase 2 GALAXI 1 study. J Crohns Colitis. 2022;16:i026-i27.

    Article  Google Scholar 

  63. D’Haens GR, Panaccione R, Panés J, Hisamatsu T, Bossuyt P, Danese S, et al. 52-weeks risankizumab subcutaneous maintenance dosing Is efficacious and well tolerated in patients with moderate to severe Crohn’s disease who had delayed response to 12-weeks IV risankizumab induction. United Eur Gastroenterol J. 2022;10:98–9.

    Google Scholar 

  64. Sandborn WJ, Ferrante M, Bhandari BR, Berliba E, Hibi T, D’Haens GR, et al. Efficacy and safety of continued treatment with mirikizumab in a phase 2 trial of patients with ulcerative colitis. Clin Gastroenterol Hepatol. 2022;20:105–15.

    Article  CAS  PubMed  Google Scholar 

  65. Efficacy and safety of mirikizumab as induction therapy in patients with moderately to severely active ulcerative colitis: results from the phase 3 LUCENT-1 study. Gastroenterol Hepatol (N Y). 2022;18:7–8.

  66. Magro F, Pai RK, Kobayashi T, Jairath V, Rieder F, Redondo I, et al. Efficacy of mirikizumab in resolving active histologic inflammation in ulcerative colitis in LUCENT-1 induction and LUCENT-2 maintenance trials. United Eur Gastroenterol J. 2022;10:335–6.

    Google Scholar 

  67. Dignass A, Danese S, Matsuoka K, Ferrante M, Long M, Redondo I, et al. Sustained symptom control with mirikizumab in patients with moderately to severely active ulcerative colitis in the LUCENT-2 maintenance trial. United Eur Gastroenterol J. 2022;10:331.

    Google Scholar 

  68. Panés J, Allegretti J, Sands BE, Huang K-HG, Kavalam M, Germinaro M, et al. The effect of guselkumab induction therapy in patients with moderately to severely active ulcerative colitis: QUASAR phase 2b induction results at week 12 by prior inadequate response or intolerance to advanced therapy. United Eur Gastroenterol J. 2022;10:87–8

  69. Filipe-Santos O, Bustamante J, Chapgier A, Vogt G, de Beaucoudrey L, Feinberg J, et al. Inborn errors of IL-12/23- and IFN-gamma-mediated immunity: molecular, cellular, and clinical features. Semin Immunol. 2006;18:347–61.

    Article  CAS  PubMed  Google Scholar 

  70. MacLennan C, Fieschi C, Lammas DA, Picard C, Dorman SE, Sanal O, et al. Interleukin (IL)-12 and IL-23 are key cytokines for immunity against Salmonella in humans. J Infect Dis. 2004;190:1755–7.

    Article  CAS  PubMed  Google Scholar 

  71. Ouederni M, Sanal O, Ikinciogullari A, Tezcan I, Dogu F, Sologuren I, et al. Clinical features of Candidiasis in patients with inherited interleukin 12 receptor β1 deficiency. Clin Infect Dis. 2014;58:204–13.

    Article  CAS  PubMed  Google Scholar 

  72. Sandborn WJ, Feagan BG, Danese S, O’Brien CD, Ott E, Marano C, et al. Safety of ustekinumab in inflammatory bowel disease: pooled safety analysis of results from phase 2/3 studies. Inflamm Bowel Dis. 2021;27:994–1007.

    Article  PubMed  Google Scholar 

  73. Papp KA, Griffiths CE, Gordon K, Lebwohl M, Szapary PO, Wasfi Y, 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;168:844–54.

    Article  CAS  PubMed  Google Scholar 

  74. Chackerian AA, Chen SJ, Brodie SJ, Mattson JD, McClanahan TK, Kastelein RA, et al. Neutralization or absence of the interleukin-23 pathway does not compromise immunity to mycobacterial infection. Infect Immun. 2006;74:6092–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Lee JS, Tato CM, Joyce-Shaikh B, Gulen MF, Cayatte C, Chen Y, et al. Interleukin-23-independent IL-17 production regulates intestinal epithelial permeability. Immunity. 2015;43:727–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Singh S, Singh S, Thangaswamy A, Thangaraju P, Varthya SB. Efficacy and safety of Risankizumab in moderate to severe psoriasis: a systematic review and meta-analysis. Dermatol Ther. 2021;34: e14487.

    Article  CAS  PubMed  Google Scholar 

  77. Bai F, Li GG, Liu Q, Niu X, Li R, Ma H. Short-term efficacy and safety of IL-17, IL-12/23, and IL-23 inhibitors brodalumab, secukinumab, ixekizumab, ustekinumab, guselkumab, tildrakizumab, and risankizumab for the treatment of moderate to severe plaque psoriasis: a systematic review and network meta-analysis of randomized controlled trials. J Immunol Res. 2019;2019:2546161.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Östör A, Van den Bosch F, Papp K, Asnal C, Blanco R, Aelion J, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from the KEEPsAKE 2 study. Rheumatology (Oxford). 2022 (e-pub ahead of print).

  79. Gordon KB, Lebwohl M, Papp KA, Bachelez H, Wu JJ, Langley RG, et al. Long-term safety of risankizumab from 17 clinical trials in patients with moderate-to-severe plaque psoriasis. Br J Dermatol. 2022;186:466–75.

    Article  CAS  PubMed  Google Scholar 

  80. Blauvelt A, Tsai TF, Langley RG, Miller M, Shen YK, You Y, et al. Consistent safety profile with up to 5 years of continuous treatment with guselkumab: pooled analyses from the phase 3 VOYAGE 1 and VOYAGE 2 trials of patients with moderate-to-severe psoriasis. J Am Acad Dermatol. 2022;86:827–34.

    Article  CAS  PubMed  Google Scholar 

  81. Ferrante M, Feagan BG, Panés J, Baert F, Louis E, Dewit O, et al. Long-term safety and efficacy of risankizumab treatment in patients with Crohn’s disease: results from the phase 2 open-label extension study. J Crohns Colitis. 2021;15:2001–10.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Blauvelt A, Papp KA, Griffiths CE, Randazzo B, Wasfi Y, Shen YK, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol. 2017;76:405–17.

    Article  CAS  PubMed  Google Scholar 

  83. Reich K, Armstrong AW, Foley P, Song M, Wasfi Y, Randazzo B, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol. 2017;76:418–31.

    Article  CAS  PubMed  Google Scholar 

  84. Reich K, Gooderham M, Thaçi D, Crowley JJ, Ryan C, Krueger JG, et al. Risankizumab compared with adalimumab in patients with moderate-to-severe plaque psoriasis (IMMvent): a randomised, double-blind, active-comparator-controlled phase 3 trial. Lancet. 2019;394:576–86.

    Article  CAS  PubMed  Google Scholar 

  85. Sands BE, Irving PM, Hoops T, Izanec JL, Gao LL, Gasink C, et al. Ustekinumab versus adalimumab for induction and maintenance therapy in biologic-naive patients with moderately to severely active Crohn’s disease: a multicentre, randomised, double-blind, parallel-group, phase 3b trial. Lancet. 2022;399:2200–11.

    Article  CAS  PubMed  Google Scholar 

  86. Norden A, Moon JY, Javadi SS, Munawar L, Maul JT, Wu JJ. Anti-drug antibodies of IL-23 inhibitors for psoriasis: a systematic review. J Eur Acad Dermatol Venereol. 2022;36:1171–7.

    Article  CAS  PubMed  Google Scholar 

  87. Bonovas S, Fiorino G, Allocca M, Lytras T, Nikolopoulos GK, Peyrin-Biroulet L, et al. Biologic therapies and risk of infection and malignancy in patients with inflammatory bowel disease: a systematic review and network meta-analysis. Clin Gastroenterol Hepatol. 2016;14:1385–97.

    Article  PubMed  Google Scholar 

  88. Chupin A, Perduca V, Meyer A, Bellanger C, Carbonnel F, Dong C. Systematic review with meta-analysis: comparative risk of lymphoma with anti-tumour necrosis factor agents and/or thiopurines in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2020;52:1289–97.

    CAS  PubMed  Google Scholar 

  89. Ferrante M, Peyrin-Biroulet L, Dignass A, Rubin DT, Danese S, D’Haens GR, et al. Clinical and endoscopic improvements with risankizumab induction and maintenance dosing versus placebo are observed irrespective of number of prior failed biologics. United Eur Gastroenterol J. 2022;10:101–2.

    Google Scholar 

  90. Barberio B, Gracie DJ, Black CJ, Ford AC. Efficacy of biological therapies and small molecules in induction and maintenance of remission in luminal Crohn’s disease: systematic review and network meta-analysis. Gut. 2023;72:264–74.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank Alexa Zayadi for helping to prepare the figure presented in this manuscript.

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Gastroenterology, Western University, London, ON, Canada

    Sudheer K. Vuyyuru, Vipul Jairath & Brian G. Feagan

  2. Alimentiv Inc., London, ON, Canada

    Sudheer K. Vuyyuru, Lisa M. Shackelton, Jurij Hanzel, Christopher Ma, Vipul Jairath & Brian G. Feagan

  3. Department of Gastroenterology, UMC Ljubljana, University of Ljubljana, Ljubljana, Slovenia

    Jurij Hanzel

  4. Division of Gastroenterology and Hepatology, Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, Canada

    Christopher Ma

  5. Department of Epidemiology and Biostatistics, Western University, London, ON, Canada

    Brian G. Feagan

Authors
  1. Sudheer K. Vuyyuru
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lisa M. Shackelton
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jurij Hanzel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christopher Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vipul Jairath
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Brian G. Feagan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brian G. Feagan.

Ethics declarations

Funding

None.

Conflict of interest

SKV is an employee of Alimentiv Inc. LMS has received consulting fees from Alimentiv Inc. JH has received speaker’s fees from Abbvie, Janssen, and Takeda, and consulting fees from Alimentiv Inc. CM has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, BioJAMP, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Takeda, Tillotts Pharma; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, Takeda; royalties from Springer Publishing; research support from Ferring, Pfizer. VJ has received consulting/advisory board fees from AbbVie, Alimentiv Inc (formerly Robarts Clinical Trials), Arena pharmaceuticals, Asieris, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genetech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Reistone Biopharma, Roche, Sandoz, Takeda, Topivert; and speaker’s fees from Abbvie, Ferring, Janssen Pfizer Shire, and Takeda. BGF has received grant/research support from Millennium Pharmaceuticals, Merck, Tillotts Pharma AG, AbbVie, Novartis Pharmaceuticals, Centocor Inc., Elan/Biogen, UCB Pharma, Bristol-Myers Squibb, Genentech, ActoGenix, and Wyeth Pharmaceuticals Inc.; consulting fees from Millennium Pharmaceuticals, Merck, Centocor Inc., Elan/Biogen, Janssen-Ortho, Teva Pharmaceuticals, Bristol-Myers Squibb, Celgene, UCB Pharma, AbbVie, Astra Zeneca, Serono, Genentech, Tillotts Pharma AG, Unity Pharmaceuticals, Albireo Pharma, Given Imaging Inc., Salix Pharmaceuticals, Novonordisk, GSK, Actogenix, Prometheus Therapeutics and Diagnostics, Athersys, Axcan, Gilead, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, GiCare Pharma Inc., and Sigmoid Pharma; and speakers bureaux fees from UCB, AbbVie, and J&J/Janssen. Alimentiv Inc. is an academic gastrointestinal contract research organization (CRO), operating under the Alimentiv Health Trust. Alimentiv Inc. provides comprehensive clinical trial services, precision medicine offerings, and centralized imaging solutions for endoscopy, histopathology, and other imaging modalities. The beneficiaries of the Alimentiv Health Trust are the employees of the enterprises it holds. LMS, JH, CM, VJ, and BGF are consultants to Alimentiv Inc.; they do not hold equity positions or shares in Alimentiv Inc. JH, CM, VJ, and BGF have a primary academic appointment.

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and material

Not applicable.

Code availability

Not applicable.

Authors contributions

VJ and BGF supervised the work. All authors drafted and critically advised the manuscript for important intellectual content, and approved the final submitted version of the work.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vuyyuru, S.K., Shackelton, L.M., Hanzel, J. et al. Targeting IL-23 for IBD: Rationale and Progress to Date. Drugs 83, 873–891 (2023). https://doi.org/10.1007/s40265-023-01882-9

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-023-01882-9

Search

Navigation