The IL23/Th17 pathway as a therapeutic target in chronic inflammatory diseases

Inflammation and Allergy - Drug Targets

Volumn 11, Issue 2, 2012, Pages 159-168

  Toussirot, Éric ^a,b  

^a UNIVERSITY HOSPITAL OF BESANÇON   (France)

^b Hôpital Saint Jacques   (France)

Author keywords

Autoimmune diseases; Briakinumab; Interleukin 12; Interleukin 17; Interleukin 23; Secukinumab; Th17; Ustekinumab

Indexed keywords

AIN 457; APILIMOD; BRIAKINUMAB; BRODALUMAB; ETANERCEPT; INFLIXIMAB; INTERLEUKIN 12; INTERLEUKIN 12 RECEPTOR; INTERLEUKIN 17; INTERLEUKIN 17F; INTERLEUKIN 21; INTERLEUKIN 22; INTERLEUKIN 23; INTERLEUKIN 23 RECEPTOR; IXEKIZUMAB; LY 2525623; MONOCLONAL ANTIBODY; PLACEBO; SECUKINUMAB; UNCLASSIFIED DRUG; USTEKINUMAB;

ADAPTIVE IMMUNITY; ANKYLOSING SPONDYLITIS; ANTIGEN PRESENTATION; AUTOIMMUNE DISEASE; CELLULAR IMMUNITY; CHRONIC INFLAMMATION; CROHN DISEASE; DIARRHEA; DISEASE ACTIVITY; DIZZINESS; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; DRUG TARGETING; HEADACHE; HUMAN; HUMORAL IMMUNITY; IMMUNOPATHOGENESIS; INFECTION; INFECTION RISK; INFLAMMATORY DISEASE; INJECTION SITE REACTION; LYMPHOCYTE DIFFERENTIATION; MULTIPLE SCLEROSIS; MYALGIA; NONHUMAN; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROTEIN FUNCTION; PROTEIN STRUCTURE; PSORIASIS; PSORIASIS VULGARIS; PSORIATIC ARTHRITIS; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECOMMENDED DRUG DOSE; RESPIRATORY TRACT INFECTION; REVIEW; RHEUMATOID ARTHRITIS; SIDE EFFECT; SORE THROAT; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TH17 CELL; TREATMENT OUTCOME; TREATMENT RESPONSE; TUBERCULOSIS; UPPER ABDOMINAL PAIN; UPPER RESPIRATORY TRACT INFECTION; UVEITIS;

EID: 84857774124     PISSN: 18715281     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152812800392805     Document Type: Review

References (60)

1. Toussirot, E.; Wendling, D. The use of TNF-alpha blocking agents in rheumatoid arthritis: an update. Expert Opin. Pharmacother., 2007, 8, 2089-2107.
2. Kikly, R.; Liu, L.; Na, S.; Sedwick, J.D. The IL-23/Th17 axis: therapeutic target for autoimmune inflammation. Curr. Opin. Immunol., 2006, 18, 670-675.
3. Iwakura, Y.; Ishigame, H. The IL-23/IL-17 axis in inflammation. J. Clin. Invest., 2006, 116, 1218-1222.
4. McGEachy, M.J.; Cua, D.J. The link between IL-23 and Th17 cellmediated immune pathologies. Semin. Immunol., 2007, 19, 372-376.
5. Tang, C.; Chen, S.; Qian, H.; Huanh, W. IL-23: as a drug for autoimmune inflammatory diseases. Immunology, 2011, Oct 17. doi: 10.1111/j.1365-2567.2011.03522.x. [Epub ahead of print].
6. Pappu, R.; Ramirez-Carrozzi, V.; Sambandam, A. The interleukin- 17 cytokine family: critical players in host defence and inflammatory diseases. Immunology, 2011, 134, 8-16.
7. Gee, K.; Guzzo, C.; Che Mat, N.F.; Ma, W.; Kumar, A. The IL-12 family of cytokines in infection, inflammation and autoimmune disorders. Inflam. Allergy-Drug Targets, 2009, 8, 40-52.
8. O. Ustekinumab. MAbs, 2009, 1, 216-221.
9. Murphy, C.A.; Langrish, C.L.; Chen, Y.; Blumenschein, W.; McClanahan, T.; Kastelein, R.A.; Sedgwick, J.D.; Cua, D.J. Divergent pro and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J. Exp. Med., 2003, 198, 1951-1957.
10. Langrish, C.L.; Chen, Y.; Blumenschein, W.M.; Mattson, J.; Basham, B.; Sedgwick, J.D.; McClanahan, T.; Kastelein, R.A.; Cua, D.J. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med., 2005, 201, 233-240.
11. Romagnani, R. Human Th17 cells. Arthritis Res. Ther., 2008, 10, 206.
12. Miossec, P.; Korn, T.; Kuchroo, V.K. Interleukin-17 and type 17 helper T cells. N. Engl. J. Med., 2009, 361, 888-898.
13. Miossec, P. IL-17 and Th17 cells in human inflammatory diseases. Microbes Infect., 2009, 11, 625-630.
14. P. Interleukin -17 in rheumatoid arthritis. If T cells were to contribute to inflammation and destruction through synergy. Arthritis Rheum., 2003, 48, 594-601.
15. Chabaud, M.; Durand, J.M.; Buchs, N.; Fossiez, F.; Page, G.; Frappart, L.; Miossec, P. Human interleukin-17: A T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum., 1999, 42, 963-970.
16. Lubberts E. IL-17/Th17 targeting: on the road to prevent chronic destructive arthritis? Cytokine, 2008, 41, 84-91.
17. Chabaud, M.; Lubberts, E.; Joosten, L.; van Den Berg, W.; Miossec, P. IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis. Arthritis Res., 2001, 3, 168-177.
18. Paradowska-Gorycka, A.; Grzybowska-Kowalczyk, A.; Wojtecka- Lukasik, E.; Maslinski, S. IL-23 in the pathogenesis of rheumatoid arthritis. Scand. J. Immunol., 2010, 71, 134-145.
19. Kim, H.R.; Kim, H.S.; Park, M.K.; Cho, M.L.; Lee, S.H.; Kim, H.Y. The clinical role of IL-23p19 in patients with rheumatoid arthritis. Scand. J. Rheumatol., 2007, 36, 259-264.
20. Nakae, S.; Nambu, A.; Sudo, K.; Iwakura, Y. Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J. Immunol., 2003, 171, 6173-6177.
21. Hill Gaston, J.S.; Goodall, J.C.; Baeten, D. Interleukin-23: a central cytokine in the pathogenesis of spondyloarthritis. Arthritis Rheum., 2011, 63, 3668-3671.
22. Yeremenko, N.; Baten, D. IL-17 in spondyloarthritis: is the T - party over? Arthritis Res. Ther., 2011, 13, 115.
23. Mei, Y.; Pan, F.; Gao, J.; Ge, R.; Duan, Z.; Zeng, Z.; Liao, F.; Xia, G.; Wang, S.; Xu, S.; Xu, J.; Zhang, L.; Ye, D. Increased serum IL- 17 and IL-23 in the patient with ankylosing spondylitis. Clin. Rheumatol., 2011, 30, 269-273.
24. Appel, H.; Maier, R.; Wu, P.; Scheer, R.; Hempfing, A.; Kayser, R.; Thiel, A.; Radbruch, A.; Loddenkemper, C.; Sieper, J. Analysis of IL-17(+) cells in facet joints of patients with spondyloarthritis suggests that the innate immune pathway might be of greater relevance than the Th17-mediated adaptive immune response. Arthritis Res. Ther., 2011, 13, R95.
25. Singh, A.K.; Misra, R.; Aggarwal, A. Th17 associated cytokines in patients with reactive arthritis/undifferentiated spondylarthropathy. Clin. Rheumatol., 2011, 30, 771-776.
26. Shaker, O.G.; Moustafa, W.; Essmat, S.; Abdel-Halim, M.; El- Komy, M. The role of interleukin-12 in the pathogenesis of psoriasis. Clin. Biochem., 2006, 39, 119-125.
27. Lee, E.; Trepicchio, W.L.; Oestreicher, J.L.; Pittman, D.; Wang, F.; Chamian, F.; Dhodapkar, M.; Krueger, JG. Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. J. Exp. Med., 2004, 199, 125-130.
28. Kopp, T.; Lenz, P.; Bello-Fernandez, C.; Kastelein, R.A.; Kupper, T.S.; Stingl, G. IL-23 production by cosecretion of endogenous p19 and transgenic p40 in keratin 14/p40 transgenic mice: evidence for enhanced cutaneous immunity. J. Immunol., 2003, 170, 5438-5444.
29. Fujino, S.; Andoh, A.; Bamba, S.; Ogawa, A.; Hata, K.; Araki, Y.; Bamba, T.; Fujiyama, Y. Increased expression of interleukin 17 in inflammatory bowel disease. Gut, 2003, 52, 65-70.
30. Elson, C.O.; Cong, Y.; Weaver, C.T.; Schoeb, T.R.; McClanahan, T.K.; Fick, R.B.; Kastelein, R.A. Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice. Gastroenterology. 2007, 132, 2359-2370.
31. Cua, D.; Sherlock, J.; Chen, Y.; Murphy, C.A.; Joyce, B.; Seymour, B.; Lucian, L.; To, W.; Kwan, S.; Churakova, T.; Zurawski, S.; Wiekowski, M.; Lira, S.A.; Gorman, D.; Kastelein, R.A. Sedgwick, J.D. Intereukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature, 2003, 421, 744-748.
32. Chen, Y.; Langrish, C.L.; McKenzie, B.; Joyce-Shaikh, B.; Stumhofer, J.S.; McClanahan, T.; Blumenschein, W.; Churakovsa, T.; Low, J.; Presta, L.; Hunter, C.A.; Kastelein, R.A.; Cua, D.J. Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis. J. Clin. Invest., 2006, 116, 1317-1326.
33. Constantinescu, C.S.; Wysocka, M.; Hilliard, B.; Ventura, E.S.; Lavi, E.; Trinchieri, G.; Rostami, A. Antibodies against IL-12 prevent superantigen-induced and spontaneous relapses of experimental autoimmune encephalomyelitis. J. Immunol., 1998, 161, 5097-5104.
34. Matusevicius, D.; Kivisäkk, P.; He, B.; Kostulas, N.; Ozenci, V.; Fredrikson, S.; Link, H. Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis. Mult. Scler., 1999, 5, 101-104.
35. Karaderi, T.; Harvey, D.; Farrar, C.; Appleton, L.H.; Stone, M.A.; Sturrock, R.D.; Brown, M.A.; Wordsworth, P.; Pointon, J.J. Association between the interleukin 23 receptor and ankylosing spondylitis is confirmed by a new UK case-control study and metaanalysis of published series. Rheumatology (Oxford), 2009, 48, 386-389.
36. Hüffmeier, U.; Lascorz, J.; Böhm, B.; Lohmann, J.; Wendler, J.; Mössner, R.; Reich, K.; Traupe, H.; Kurrat, W.; Burkhardt, H.; Reis, A. Genetic variants of the IL-23R pathway: association with psoriatic arthritis and psoriasis vulgaris, but no specific risk factor for arthritis. J. Invest. Dermatol., 2009, 129, 355-358.
37. Orozco, G.; Rueda, B.; Robledo, G.; García, A.; Martín, J. Investigation of the IL23R gene in a Spanish rheumatoid arthritis cohort. Hum. Immunol., 2007, 68, 681-684.
38. Kurzeja, M.; Rudnicka, L.; Olszewska, M. New interleukin-23 pathway inhibitors in dermatology. Ustekinumab, briakinumab and secukinumab. Am. J. Clin. Dermatol., 2011, 12, 113-125.
39. Gonzalez-Gonzlez, L.A.; Foster, C.S. Secukinumab. Drugs Future, 2011, 36, 441-445.
40. Elliott, M.; Benson, J.; Blank, M.; Brodmerkel, C.; Baker, D.; Ruley Sharples, K.; Szapary, P. Ustekinumab: lessons from targeting interleukin-12/23p40 in immune mediated diseases. Ann. NY Acad. Sci., 2009, 1182, 97-110.
41. Segal, B.M.; Constantinescu, C.S.; Raychaudhuri, A.; Kim, L.; Fidelus-Gort, R.; Kasper, L.H.; Ustekinumab MS Investigators. Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: a phase II, double-blind, placebo-controlled, randomised, dose-ranging study. Lancet Neurol., 2008, 7, 796-804.
42. Leonardi, C.L.; Kimball, A.B.; Papp, K.A.; Yeilding, N.; Guzzo, C.; Wang, Y.; Li, S.; Dooley, L.T.; Gordon, K.B.; PHOENIX 1 study investigators.Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebocontrolled trial (PHOENIX 1). Lancet, 2008, 371, 1665-1674.
43. Papp, K.A.; Langley, R.G.; Lebwohl, M.; Krueger, G.G.; Szapary, P.; Yeilding, N.; Guzzo, C.; Hsu, M.C.; Wang, Y.; Li, S.; Dooley, L.T.; Reich, K.; PHOENIX 2 study investigators. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet, 2008, 371, 1675-1684.
44. Griffiths, C.E.; Strober, B.E.; van de Kerkhof, P.; Ho, V.; Fidelus- Gort, R.; Yeilding, N.; Guzzo, C.; Xia, Y.; Zhou, B.; Li, S.; Dooley, L.T.; Goldstein, N.H.; Menter, A.; ACCEPT Study Group. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N. Engl. J. Med., 2010, 362, 118-128.
45. Gottlieb, A.; Menter, A.; Medelsohn, A.; Shen, Y.K.; Li, S.; Guzzo, C.; Fretzin, S.; Kunynetz, R.; Kavanaugh, A. Ustekinumab, a human interleukin 12/23 monoclonal antibody for psoriatic arthritis: randomized, double blind, placebo controlled, cross-over trial. Lancet, 2009, 373, 633-640.
46. Kavanaugh, A.; Menter, A.; Mendelsohn, A.; Shen, Y.K.; Lee, S.; Gottlieb, A.B. Effect of ustekinumab on physical function and health-related quality of life in patients with psoriatic arthritis: a randomized, placebo-controlled, phase II trial. Curr. Med. Res. Opin., 2010, 26, 2385-2392.
47. Sandborn, W.J.; Feagan, B.G.; Fedorak, R.N.; Scherl, E.; Fleisher, M.R.; Katz, S.; Johanns, J.; Blank, M.; Rutgeerts P.; for the Ustekinumab Crohn's Disease Study Group. A randomized trial of Ustekinumab, a human interleukin-12/23 monoclonal antibody in patients with moderate-to-severe Crohn's disease. Gastroenterology, 2008, 135, 1130-1141.
48. Segal, B.M.; Constantinescu, C.S.; Raychaudhuri, A.; Kim, L.; Fidelus-Gort, R.; Kasper, L.H. Ustekinumab MS Investigators.Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsingremitting multiple sclerosis: a phase II, double-blind, placebocontrolled, randomised, dose-ranging study. Lancet Neurol., 2008, 7, 796-804.
49. Longbrake, E.; Racke, M.K. Why did IL-12/IL-23 antibody therapy fail in multiple sclerosis? Expert Rev. Neurother., 2009, 9, 319-321.
50. Hueber, W.; Patel, D.D.; Dryja, T.; Wright, A.M.; Korovela, I.; Bruin, G.; Antoni, C.; Draelos, Z.; Gold, M.H.; the psoriasis study group. Effects of AIN457, a fully human antibody to interleukin- 17A on psoriasis, rheumatoid arthritis and uveitis. Sci. Trans. Med., 2010, 52, 1-9.
51. Genovese, M.C.; Durez, P.; Richards, H.B.; Supronik, J.; Dokoupilova, E.; Mpofu, S. One Year Efficacy and Safety Results of a Phase II Trial of Secukinumab in Patients with Rheumatoid Arthritis. Arthritis Rheum., 2011, 63 (Suppl), S149-S150.
52. Baeten, D.; Sieper, J.; Emery, P.; Braun, J.; van der Heijde, D.; McInnes, I.; van Laar, J.; Landewe, R.; Wordsworth, P.; Wollenhaupt, J.; Kellner, H.; Paramarta, J.; Bertolino, A.; Wright, A.; Hueber, W. The anti-IL-17A monoclonal antibody secukinulab (AIN457) showed good safety and efficacy in the treatment of active ankylosing spondylitis. Ann. Rheum. Dis., 2011, 70 (Suppl3), 127.
53. Baraliakos, X.; Braun, J.; Laurent, D.D.; Baeten, D.; van der Heijde, D.; Sieper, J.; Emery, P.; McInnes, I.; van Laar, J.; Landewe, R.; Wordsworth, P.; Wollenhaupt, J.; Kellner, H.; Wright, A.M.; Gsteiger, S.; Hueber, W. Interleukin-17A blockade with secukinumab reduces spinal inflammation in patients with ankylosing spondylitis as early as week 6, as detected by magnetic resonance imaging. Arthritis Rheum., 2011, 63 (Suppl), S972.
54. McInnes, I.; Sieper, J.; Braun, J.; Emery, P.; van der Heijde, D.; Isaacs, J.; Dahmen, G.; Wollenhaupt, J.; Schulze-Koops, H.; Gsteiger, S.; Bertolino, A.; Hueber, W.; Tak, P.P. Anti-Interleukin 17A monoclonal antibody secukinumab reduces signs and symptoms of psoriatic arthritis in a 24-Week multicenter, doubleblind, randomized, placebo-controlled trial. Arthritis Rheum., 2011, 63 (Suppl), S306.
55. Kimball, A.B.; Gordon, K.B.; Langley, R.G.; Menter, A.; Chartash, E.K.; Valdes, J.; ABT-874 Psoriasis Study Investigators. Safety and efficacy of ABT-874, a fully human interleukin 12/23 monoclonal antibody, in the treatment of moderate to severe chronic plaque psoriasis: results of a randomized, placebocontrolled, phase 2 trial. Arch. Dermatol., 2008, 144, 200-207.
56. Gordon, K.B.; Langley, R.G.; Gottlieb, A.B.; Papp, K.A.; Krueger, G.G.; Strober, B.E.; Williams, D.A.; Gu, Y.; Valdes, J.M. A Phase III, Randomized, Controlled Trial of the Fully Human IL-12/23 mAb Briakinumab in Moderate-to-Severe Psoriasis. J Invest Dermatol. 2011 Oct 20. doi: 10.1038/jid.2011.304. [Epub ahead of print].
57. Sands, B.E.; Jacobson, E.W.; Sylwestrowicz, T.; Younes, Z.; Dryden, G.; Fedorak, R.; Greenbloom, S. Randomized, doubleblind, placebo-controlled trial of the oral interleukin-12/23 inhibitor apilimod mesylate for treatment of active Crohn's disease. Inflamm. Bowel Dis., 2010, 16, 1209-1218.
58. [Krausz, S.; Boumans, M.J.; Gerlag, D.M.; Lufkin, J.; van Kuijk, A.W.; Bakker, A.; de Boer M.; Lodde, B.M.; Reedquist, K.A.; Jacobson, E.W.; O'Meara, M.; Tak, P.P. A phase IIa, randomized, double-blind, placebo-controlled trial of apilimod mesylate, an IL- 12/IL-23 inhibitor, in patients with rheumatoid arthritis. Arthritis Rheum., 2011 Dec 14. doi: 10.1002/art.34339. [Epub ahead of print].
59. Genovese, M.; Van den Bosch, F.; Roberson, S.A.; Bojin, S.; Biagini, I.M.; Ryan, P.; Sloan-Lancaster, J. LY2439821, a humanized anti-interleukin-17 monoclonal antibody in the treatment of patients with rheumatoid arthritis: a phase I randomized double blind placebo controlled proof of concept study. Arthritis Rheum., 2010, 62, 929-939.
60. Genovese, M.C.; Greenwald, M.W.; Cho, C.S.; Berman, A.; Jin, L.; Cameron, G.; Xie, L.; Braun, D.; Banerjee, S.; Warner, L. A Phase 2 study of multiple subcutaneous doses of LY2439821, an anti-IL- 17 monoclonal antibody, in patients with rheumatoid arthritis in two populations: naïve to biologic therapy or inadequate responders to tumor necrosis factor alpha inhibitors. Arthritis Rheum., 2011, 63 (Suppl), S1017.