Top

17-03-2015 | Psoriatic arthritis | Review | Article

Ustekinumab in the Treatment of Psoriasis and Psoriatic Arthritis

Journal: Rheumatology and Therapy

Authors: Laura J. Savage, Miriam Wittmann, Dennis McGonagle, Philip S. Helliwell

Publisher: Springer Healthcare

Abstract

Biologics have revolutionized the therapy of the psoriatic disease spectrum. These new classes of drugs also allow deeper insight into the pathogenesis of the disease and highlight the existence of distinct “molecular” disease subgroups as evidenced by the spectrum of clinical response seen. Molecules associated with both the interleukin (IL)-17 and interferon (IFN)γ pathways have important functions in psoriatic inflammation, and both are targeted by drugs acting on the p40 subunit shared by IL-12 and IL-23. These IL-12 family members are upstream of pathways characterized by the production of IFNγ and IL-17 related molecules, including IL-17, IL-22, and CCL20. We here summarize the mode of action and clinical studies of the p40 inhibitor ustekinumab with focus on both psoriasis and psoriatic arthritis.

Chiricozzi A, Guttman-Yassky E, Suárez-Fariñas M, et al. Integrative responses to IL-17 and TNF-alpha in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis. J Invest Dermatol. 2011;131:677–87.PubMedCrossRef

Vignali DA, Kuchroo VK. IL-12 family cytokines: immunological playmakers. Nature immunol. 2012;13:722–8.CrossRef

O’Rielly DD, Rahman P. Genetics of susceptibility and treatment response in psoriatic arthritis. Nat Rev Rheumatol. 2011;7:718–32.PubMedCrossRef

Wu CY, Gadina M, Wang K, O’Shea J, Seder RA. Cytokine regulation of IL-12 receptor beta2 expression: differential effects on human T and NK cells. Eur J Immunol. 2000;30:1364–74.PubMedCrossRef

Nishikomori R, Usui T, Wu CY, Morinobu A, O’Shea JJ, Strober W. Activated STAT4 has an essential role in Th1 differentiation and proliferation that is independent of its role in the maintenance of IL-12R beta 2 chain expression and signaling. J Immunol. 2002;169:4388–98.PubMedCrossRef

Trinchieri G, Pflanz S, Kastelein RA. The IL-12 family of heterodimeric cytokines: new players in the regulation of T cell responses. Immunity. 2003;19:641–4.PubMedCrossRef

Reddy M, Davis C, Wong J, Prabhakar U. Cutaneous lymphocyte antigen expression on activated lymphocytes and its association with IL-12R (beta1 and beta2), IL-2Ralpha, and CXCR3. Cell Immunol. 2005;236:131–9.PubMedCrossRef

Leung DY, Gately M, Trumble A, Ferguson-Darnell B, Schlievert PM, Picker LJ. Bacterial superantigens induce T cell expression of the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen, via stimulation of interleukin 12 production. J Exp Med. 1995;181:747–53.PubMedCrossRef

Smits HH, van Rietschoten JG, Hilkens CM, et al. IL-12-induced reversal of human Th2 cells is accompanied by full restoration of IL-12 responsiveness and loss of GATA-3 expression. Eur J Immunol. 2001;31:1055–65.PubMedCrossRef

10.

Aggarwal S, Ghilardi N, Xie MH, 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;278:1910–4.PubMedCrossRef

11.

Wilson NJ, et al. Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol. 2007;8:950–7.PubMedCrossRef

12.

Langrish CL, et al. IL-12 and IL-23: master regulators of innate and adaptive immunity. Immunol Rev. 2004;202:96–105.PubMedCrossRef

13.

Powell J, et al. Acute Systemic Sarcoidosis Complicating Ustekinumab Therapy For Chronic Plaque Psoriasis. Br J Dermatol. 2014.

14.

Judson MA, et al. Safety and efficacy of ustekinumab or golimumab in patients with chronic sarcoidosis. Eur Respir J. 2014;44:1296–307.PubMedCrossRef

15.

Cosgarea I, Lovric Z, Korber A, Dissemond J. Successful treatment of refractory pyoderma gangrenosum with ustekinumab only after excision of renal cell carcinoma. Int Wound J. 2014.

16.

Guenova E, et al. Interleukin 23 expression in pyoderma gangrenosum and targeted therapy with ustekinumab. Arch Dermatol. 2011;147:1203–5.PubMedCrossRef

17.

Martin-Ezquerra G, et al. Use of biological treatments in patients with hidradenitis suppurativa. J Eur Acad Dermatol Venereol: JEADV. 2014.

18.

Gulliver WP, Jemec GB, Baker KA. Experience with ustekinumab for the treatment of moderate to severe hidradenitis suppurativa. J Eur Acad Dermatol Venereol: JEADV. 2012;26:911–4.PubMedCrossRef

19.

Firinu D, et al. Biological treatments for SAPHO syndrome: an update. Inflamm Allergy Drug Targets. 2014;13:199–205.PubMedCrossRef

20.

Eytan O, Sarig O, Sprecher E, van Steensel MA. Clinical response to ustekinumab in familial pityriasis rubra pilaris caused by a novel mutation in CARD14. Br J Dermatol. 2014;171:420–2.PubMedCrossRef

21.

Di Stefani A, et al. Long-term ustekinumab treatment for refractory type I pityriasis rubra pilaris. J Dermatol Case Rep. 2013;7:5–9.PubMedCentralPubMedCrossRef

22.

Ruiz Villaverde R, Sanchez Cano D. Successful treatment of type 1 pityriasis rubra pilaris with ustekinumab therapy. European journal of dermatology : EJD. 2010;20:630–1.PubMed

23.

Wohlrab J, Kreft B. Treatment of pityriasis rubra pilaris with ustekinumab. Br J Dermatol. 2010;163:655–6.PubMedCrossRef

24.

Gottlieb AB, et al. A phase 1, double-blind, placebo-controlled study evaluating single subcutaneous administrations of a human interleukin-12/23 monoclonal antibody in subjects with plaque psoriasis. Curr Med Res Opin. 2007;23:1081–92.PubMedCrossRef

25.

Kauffman CL, et al. A phase I study evaluating the safety, pharmacokinetics, and clinical response of a human IL-12 p40 antibody in subjects with plaque psoriasis. J Invest Dermatol. 2004;123:1037–44.PubMedCrossRef

26.

Toichi E, et al. An anti-IL-12p40 antibody down-regulates type 1 cytokines, chemokines, and IL-12/IL-23 in psoriasis. J Immunol. 2006;177:4917–26.PubMedCrossRef

27.

Krueger GG, et al. A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. N Engl J Med. 2007;356:580–92.PubMedCrossRef

28.

Leonardi CL, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet. 2008;371:1665–74.PubMedCrossRef

29.

Papp KA, et al. 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;371:1675–84.PubMedCrossRef

30.

Griffiths CE, et al. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med. 2010;362:118–28.PubMedCrossRef

31.

Kimball AB, et al. Long-term efficacy of ustekinumab in patients with moderate-to-severe psoriasis treated for up to 5 years in the PHOENIX 1 study. J Eur Acad Dermatol Venereol: JEADV. 2013;27:1535–45.PubMedCrossRef

32.

Papp KA, 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.PubMedCrossRef

33.

Klaassen KM, van de Kerkhof PC, Pasch MC. Nail psoriasis: a questionnaire-based survey. Br J Dermatol. 2013;169:314–9.PubMedCrossRef

34.

de Jong EM, Seegers BA, Gulinck MK, Boezeman JB, van de Kerkhof PC. Psoriasis of the nails associated with disability in a large number of patients: results of a recent interview with 1,728 patients. Dermatology. 1996;193:300–3.PubMedCrossRef

35.

Rich P, et al. Ustekinumab improves nail disease in patients with moderate-to-severe psoriasis: results from PHOENIX 1. Br J Dermatol. 2014;170:398–407.PubMedCrossRef

36.

Tsai TF, et al. Efficacy and safety of ustekinumab for the treatment of moderate-to-severe psoriasis: a phase III, randomized, placebo-controlled trial in Taiwanese and Korean patients (PEARL). J Dermatol Sci. 2011;63:154–63.PubMedCrossRef

37.

Igarashi A, et al. Efficacy and safety of ustekinumab in Japanese patients with moderate-to-severe plaque-type psoriasis: long-term results from a phase 2/3 clinical trial. The Journal of dermatology. 2012;39:242–52.PubMedCrossRef

38.

Warren RB, Griffiths CEM. The potential of pharmacogenetics in optimizing the use of methotrexate for psoriasis. Br J Dermatol. 2005;153:869–73.PubMedCrossRef

39.

Talamonti M, et al. Pharmacogenetics of psoriasis: HLA-Cw6 but not LCE3B/3C deletion nor TNFAIP3 polymorphism predisposes to clinical response to interleukin 12/23 blocker ustekinumab. Br J Dermatol. 2013;169:458–63.PubMedCrossRef

40.

Chiu HY, et al. Human leucocyte antigen-Cw6 as a predictor for clinical response to ustekinumab, an interleukin-12/23 blocker, in Chinese patients with psoriasis: a retrospective analysis. Br J Dermatol. 2014;171:1181–8.PubMedCrossRef

41.

Naldi L, et al. Cigarette Smoking, Body Mass Index, and Stressful Life Events as Risk Factors for Psoriasis: Results from an Italian Case-Control Study. J Investig Dermatol. 2005;125:61–7.PubMedCrossRef

42.

Hamminga E, van der Lely A, Neumann H, Thio H. Chronic inflammation in psoriasis and obesity: Implications for therapy. Med Hypotheses. 2006;67(4):768–73.PubMedCrossRef

43.

Lebwohl M, et al. Impact of weight on the efficacy and safety of ustekinumab in patients with moderate to severe psoriasis: Rationale for dosing recommendations. J Am Acad Derm. 2010;63:571–9.PubMedCrossRef

44.

Lebwohl M, et al. Ustekinumab improves health-related quality of life in patients with moderate-to-severe psoriasis: results from the PHOENIX 1 trial. Br J Dermatol. 2010;162:137–46.PubMedCrossRef

45.

Langley RG, et al. Ustekinumab significantly improves symptoms of anxiety, depression, and skin-related quality of life in patients with moderate-to-severe psoriasis: Results from a randomized, double-blind, placebo-controlled phase III trial. J Am Acad Dermatol. 2010;63:457–65.PubMedCrossRef

46.

Guenther L, et al. Impact of ustekinumab on health-related quality of life and sexual difficulties associated with psoriasis: results from two phase III clinical trials. J Eur Acad Dermatol Venereol: JEADV. 2011;25:851–7.PubMedCrossRef

47.

McInnes IB, et al. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double blind, placebo-controlled PSUMMIT 1 trial. Lancet. 2013;382:780–9.PubMedCrossRef

48.

Ritchlin C, et al. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial. Ann Rheum Dis. 2014;73:990–9.PubMedCentralPubMedCrossRef

49.

Kavanaugh A, et al. Ustekinumab, an anti-IL-12/23 p40 monoclonal antibody, inhibits radiographic progression in patients with active psoriatic arthritis: results of an integrated analysis of radiographic data from the phase 3, multicentre, randomised, double-blind, placebo-controlled PSUMMIT-1 and PSUMMIT-2 trials. Ann Rheum Dis. 2014;73:1000–6.PubMedCentralPubMedCrossRef

50.

McInnes IB, et al. Safety of ustekinumab from the placebo controlled periods of psoriatic arthritis and psoriasis clinical development programs. Arth Rheum. 2013;65:S138.

51.

Kalb R, et al. Serious infection events in the psoriasis longitudinal assessment and registry study: cumulative experience. Arthr Rheum. 2014;66(11):S814 Supplement.

52.

Kavanaugh A, et al. Integrated Safety of Ustekinumab in psoriatic arthritis: 2 year follow-up from the psoriatic arthritis clinical development program. Arthr Rheum. 2014;66(11):S686 Supplement.

53.

Poddubnyy D, Callhoff J, Listing J, Sieper J. Ustekinumab for the treatment of patients with active ankylosing spondylitis: results of a 28 week, prospective, open label, proof of concept study (TOPAS). Arthr Rheum. 2013;65:S766.

54.

Poddubnyy D, Hermann K-G, Callhoff J, Listing J, Sieper J. Impact of ustekinumab on active inflammation and post-inflammatory structural changes as detected by magnetic resonance imaging in patients with active ankylosing spondylitis: results of a 28-Week, prospective, open-label, proof-of-concept study. Arthr Rheum. 2014;66(11):S1145 Supplement.

55.

Viguier M, et al. Onset of psoriatic arthritis in patients treated with efalizumab for moderate to severe psoriasis. Arthritis Rheum. 2008;58:1796–802.PubMedCrossRef

Medicine Matters Rheumatology

Abstract