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Tildrakizumab: A Review in Moderate-to-Severe Plaque Psoriasis

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Abstract

Tildrakizumab (tildrakizumab-asmn in the USA) [Ilumetri®; Ilumya™] is a humanized monoclonal antibody (mAb) that selectively targets the p19 subunit of interleukin (IL)-23, thereby inhibiting the IL-23/IL-17 axis, the signalling pathway primarily implicated in the immunopathogenesis of psoriasis. Administered subcutaneously, it is approved for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy (e.g. in the EU and Australia) and those who are candidates for systemic therapy or phototherapy (in the USA). In the pivotal phase III reSURFACE 1 and 2 trials, tildrakizumab was superior to placebo and efficacious compared with etanercept, in terms of the proportion of patients achieving a response [≥ 75% improvement from baseline in Psoriasis Area and Severity index score (PASI 75) and a Physician’s Global Assessment score of 0/1] at week 12. Response rates peaked at week 22 and the vast majority of patients achieving PASI 75 at week 28 maintained this response after a total of 3 years of treatment in the reSURFACE trials and their ongoing open-label extension studies. In addition, patients with a partial or no response to etanercept at week 28 benefitted from switching to the highest approved dose of tildrakizumab in the reSURFACE 2 trial and its ongoing extension. Treatment with tildrakizumab improved health-related quality of life and was generally well tolerated, both in the short- and longer-term. Tildrakizumab thus expands the range of useful therapeutic options for patients with moderate-to-severe plaque psoriasis, particularly those with an inadequate response to phototherapy and conventional systemic agents.

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References

  1. Boehncke WH, Schön MP. Psoriasis. Lancet. 2015;386(9997):983–94.

    Article  CAS  Google Scholar 

  2. Hawkes JE, Chan TC, Krueger JG. Psoriasis pathogenesis and the development of novel, targeted immune therapies. J Allergy Clin Immunol. 2017;140(3):645–53.

    Article  CAS  Google Scholar 

  3. Feldman SR, Goffe B, Rice G, et al. The challenge of managing psoriasis: unmet medical needs and stakeholder perspectives. Am Health Drug Benefits. 2016;9(9):504–13.

    PubMed  PubMed Central  Google Scholar 

  4. Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008;58(5):826–50.

    Article  Google Scholar 

  5. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: case-based presentations and evidence-based conclusions. J Am Acad Dermatol. 2011;65(1):137–74.

    Article  Google Scholar 

  6. National Institute for Health and Care Excellence (NICE). Psoriasis: assessment and management. 2012. https://www.nice.org.uk. Accessed 16 Jan 2019.

  7. Nast A, Gisondi P, Ormerod AD, et al. European S3-guidelines on the systemic treatment of psoriasis vulgaris—update 2015—short version—EDF in cooperation with EADV and IPC. J Eur Acad Dermatol Venereol. 2015;29:2277–94.

    Article  CAS  Google Scholar 

  8. Kolios AGA, Yawalkar N, Anliker M, et al. Swiss S1 guidelines on the systemic treatment of psoriasis vulgaris. Dermatology. 2016;232:385–406.

    Article  Google Scholar 

  9. Mrowietz U, Kragballe K, Reich K, et al. Definition of treatment goals for moderate to severe psoriasis: a European consensus. Arch Dermatol Res. 2011;303(1):1–10.

    Article  CAS  Google Scholar 

  10. Gisondi P, Del Giglio M, Girolomoni G. Treatment approaches to moderate to severe psoriasis. Int J Mol Sci. 2017;18:2427.

    Article  Google Scholar 

  11. Feldman SR, Burudpakdee C, Gala S, et al. The economic burden of psoriasis: a systematic literature review. Expert Rev Pharmacoecon Outcomes Res. 2014;14(5):685–705.

    Article  Google Scholar 

  12. Chan TC, Hawkes JE, Krueger JG. Interleukin 23 in the skin: role in psoriasis pathogenesis and selective interleukin 23 blockade as treatment. Ther Adv Chronic Dis. 2018;9(5):111–9.

    Article  CAS  Google Scholar 

  13. Tonini A, Gualtieri B, Panduri S, et al. A new class of biologic agents facing the therapeutic paradigm in psoriasis: anti-IL-23 agents. Expert Opin Biol Ther. 2018;18(2):135–48.

    Article  CAS  Google Scholar 

  14. Fragoulis GE, Siebert S, McInnes IB. Therapeutic targeting of IL-17 and IL-23 cytokines in immune-mediated diseases. Ann Rev Med. 2016;67:337–53.

    Article  CAS  Google Scholar 

  15. Rønholt K, Iversen L. Old and new biological therapies for psoriasis. Int J Mol Sci. 2017;18:2297.

    Article  Google Scholar 

  16. Jeon C, Sekhon S, Yan D, et al. Monoclonal antibodies inhibiting IL-12, -23, and -17 for the treatment of psoriasis. Hum Vaccin Immunother. 2017;13(10):2247–59.

    Article  Google Scholar 

  17. Markham A. Tildrakizumab: first global approval. Drugs. 2018;78(8):845–9.

    Article  CAS  Google Scholar 

  18. European Medicines Agency. IlumetriTM (tildrakizumab): EU summary of product characteristics. 2018. https://www.ema.europa.eu. Accessed 15 Oct 2018.

  19. Sun Pharma ANZ Pty Ltd. Ilumya™ (tildrakizumab): Australian product information. 2018. https://www.ebs.tga.gov.au. Accessed 19 Feb 2019.

  20. Sun Pharmaceutical Industries Inc. Ilumya™ (Tildrakizumab-asmn) US prescribing information. 2018. https://www.accessdata.fda.gov. Accessed 15 Oct 2018.

  21. Hawkes JE, Yan BY, Chan TC, et al. Discovery of the IL-23/IL-17 signaling pathway and the treatment of psoriasis. J Immunol. 2018;201(6):1605–13.

    Article  CAS  Google Scholar 

  22. Di Meglio P, Nestle OF. The role of IL-23 in the immunopathogenesis of psoriasis. F1000 Biol Rep. 2010;2:40.

    PubMed  PubMed Central  Google Scholar 

  23. Kopp T, Riedl E, Bangert C, et al. Clinical improvement in psoriasis with specific targeting of interleukin-23. Nature. 2015;521(7551):222–6.

    Article  CAS  Google Scholar 

  24. Zandvliet A, Glasgow S, Horowitz A, et al. Tildrakizumab, a novel anti-IL-23 monoclonal antibody, is unaffected by ethnic variability in Caucasian, Chinese, and Japanese subjects. Int J Clin Pharmacol Ther. 2015;53(2):139–46.

    Article  CAS  Google Scholar 

  25. Khalilieh S, Hussain A, Montgomery D, et al. Effect of tildrakizumab (MK-3222), a high affinity, selective anti-IL23p19 monoclonal antibody, on cytochrome P450 metabolism in subjects with moderate to severe psoriasis. Br J Clin Pharmacol. 2018;84(10):2292–302.

    Article  CAS  Google Scholar 

  26. Khalilieh S, Hodsman P, Xu C, et al. Pharmacokinetics of tildrakizumab (MK-3222), an anti-IL-23 monoclonal antibody, following intravenous or subcutaneous administration in healthy subjects. Basic Clin Pharmacol Toxicol. 2018;123(3):294–300.

    Article  CAS  Google Scholar 

  27. European Medicines Agency. Assessment report. Ilumetri. International non-proprietary name: tildrakizumab. Procedure no. EMEA/H/C/004514/0000. 2018. https://www.ema.europa.eu. Accessed 12 Dec 2018.

  28. Reich K, Papp KA, Blauvelt A, et al. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials. Lancet. 2017;390(10091):276–88.

    Article  CAS  Google Scholar 

  29. Papp K, Thaci D, Reich K, et al. Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial. Br J Dermatol. 2015;173(4):930–9.

    Article  CAS  Google Scholar 

  30. Papp K, Reich K, Blauvelt A, et al. Efficacy of tildrakizumab for moderate-to-severe chronic plaque psoriasis: pooled analysis of 3 randomised controlled studies at weeks 12 and 28 [abstract]. Australas J Dermatol. 2018;59(Suppl 1):108–9.

    Google Scholar 

  31. Poulin Y, Ramon M, Rosoph L, et al. Efficacy of tildrakizumab in patient subgroups across a phase 2b and 2 phase 3 trials in patients with moderate to severe chronic plaque psoriasis [e-poster 10042]. In: AAD Annual Meeting. 2019.

  32. Griffiths CEM, Thaci D, Iversen L, et al. Tildrakizumab results in significant and sustained improvements in health-related quality of life in patients with moderate to severe psoriasis in a phase 3 trial (reSURFACE 1) [e-poster 8047]. In: AAD Annual Meeting. 2019.

  33. Blauvelt A, Sofen H, Papp, K, et al. Tildrakizumab efficacy over time stratified by week-28 response levels and by prior biologic use [e-poster 9874]. In: AAD Annual Meeting. 2019.

  34. Reich K, Griffiths C, Iversen L, et al. Improvements in dermatology-specific health-related quality of life in patients with moderate-to-severe psoriasis treated with tildrakizumab: pooled results from reSURFACE 1 and reSURFACE 2 phase 3 trials [abstract]. In: 27th EADV Congress. 2018.

  35. Elewski B, Menter A, Crowley J, et al. Sustained and improved efficacy of tildrakizumab from week 28 to week 52 in treating moderate-to-severe plaque psoriasis [poster]. Skin. 2018;2(Suppl 2):S22.

    Google Scholar 

  36. Crowley J, Papp KA, Hong CH, et al. Efficacy of tildrakizumab in etanercept partial or nonresponders [abstract no. AB0903]. Ann Rheum Dis. 2018;77(Suppl 2):1575–6.

    Google Scholar 

  37. Papp K, Cichanowitz N, Green S, et al. Maintenance of treatment response in chronic plaque psoriasis patients continuing treatment or discontinuing treatment with tildrakizumab in a 64-week, randomized controlled, phase 3 trial [abstract no. 4855]. J Am Acad Dermatol. 2017;76(6 Suppl 1):AB164.

    Google Scholar 

  38. Leonardi C, Menter AM, Draelos Z, et al. Impact of body weight on efficacy of tildrakizumab in moderate to severe plaque psoriasis (e-poster 10089). In: AAD Annual Meeting. 2019.

  39. Lebwohl MG, Leonardi C, Mehta NN, et al. Tildrakizumab efficacy and drug survival by metabolic syndrome status in psoriasis: post hoc analysis of 2 Phase 3 Clinical Studies (reSURFACE 1 and reSURFACE 2) [e-poster 10048]. In: AAD Annual Meeting. 2019.

  40. Papp K, Reich K, Blauvelt A, et al. Clinical efficacy of tildrakizumab in patients with chronic plaque psoriasis over 2 years of treatment: results from long-term extensions to 2 phase 3 clinical studies [poster]. In: 13th Winter Clinical Dermatology Conference. 2018.

  41. Tyring SK, Spelman L, Igarashi A, et al. Efficacy and safety of long-term tildrakizumab for plaque psoriasis: 3-year results from reSURFACE 1 [e-poster 10508]. In: AAD Annual Meeting. 2019.

  42. Gooderham M, Papp KA, Blauvelt A, et al. Efficacy and safety of long-term tildrakizumab for plaque psoriasis: 3-year results from reSURFACE 2 [e-poster 10510]. In: AAD Annual Meeting. 2019.

  43. Thaci D, Iversen L, Pau-Charles I, et al. Long-term efficacy and safety of tildrakizumab in patients with moderate-to-severe psoriasis who were responders at week 28: pooled analysis through 3 years (148 weeks) from reSURFACE 1 and reSURFACE2 phase 3 trials [abstract]. In: 27th EADV Congress. 2018.

  44. Thaci D, Griffiths CEM, Iversen L, et al. Long-term efficacy of tildrakizumab in patients with moderate to severe psoriasis who were nonresponders or partial responders to etanercept in the phase 3 reSURFACE 2 trial [e-poster 9754]. In: AAD Annual Meeting. 2019.

  45. Blauvelt A, Reich K, Papp KA, et al. Safety of tildrakizumab for moderate-to-severe plaque psoriasis: pooled analysis of three randomized controlled trials. Br J Dermatol. 2018;179(3):615–22.

    Article  CAS  Google Scholar 

  46. Sobell JM, Johnson S, Rozzo SJ, et al. Incidence of opportunistic infections in the tildrakizumab psoriasis clinical development program [e-poster 9753]. In: AAD Annual Meeting. 2019.

  47. Leonardi C, Mehta NN, Lebwohl MG, et al. Safety of tildrakizumab in patients with preexisting metabolic syndrome: post hoc analysis of 2 phase 3 clinical studies (reSURFACE 1 and reSURFACE 2) [e-poster 10556]. In: AAD Annual Meeting. 2019.

  48. Lebwohl MG, West DT, Mendelsohn AM, et al. No increased risk of liver dysfunction from tildrakizumab treatment: post hoc analyses of the tildrakizumab psoriasis clinical program [e-poster 9823]. I: ADD Annual Meeting. 2019.

  49. Glover H, Kucera K, Mendelsohn AM, et al. Limited changes in hematological parameters during tildrakizumab treatment: post hoc analysis of data from the tildrakizumab psoriasis clinical program [e-poster 10549]. In: AAD Annual Meeting. 2019.

  50. Reich K, Kimball AB, Li Q, et al. Immunogenicity with tildrakizumab, an anti-IL-23p19 monoclonal antibody, in a pooled analysis of three randomized controlled trials in patients with chronic plaque psoriasis [abstract no. 6137]. J Am Acad Dermatol. 2018;79(3 Suppl 1):AB157.

    Google Scholar 

  51. Bansback N, Sizto S, Sun H, et al. Efficacy of systemic treatments for moderate to severe plaque psoriasis: systematic review and meta-analysis. Dermatology. 2009;219(3):209–18.

    Article  CAS  Google Scholar 

  52. Sbidian E, Chaimani A, Garcia-Doval I, et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database Syst Rev. 2017;12:CD011535.

    PubMed  Google Scholar 

  53. Gniadecki R, Kragballe K, Dam TN, et al. Comparison of drug survival rates for adalimumab, etanercept and infliximab in patients with psoriasis vulgaris. Br J Dermatol. 2011;164:1091–6.

    Article  CAS  Google Scholar 

  54. Lis K, Kusawinska O, Bałkowiec-Iskra I. Tumour necrosis factor inhibitors: state of knowledge. Arch Med Sci. 2014;10(6):1175–85.

    Article  CAS  Google Scholar 

  55. Fiorentino D, Ho V, Lebwohl MG, et al. Risk of malignancy with systemic psoriasis treatment in the Psoriasis Longitudinal Assessment Registry. J Am Acad Dermatol. 2017;77:845–54.

    Article  Google Scholar 

  56. European Medicines Agency. Tremfya 100 mg solution for injection: EU summary of product characteristics. 2017. https://www.ema.europa.eu. Accessed 19 Feb 2019.

  57. European Medicines Agency. Cosentyx 150 mg powder for solution for injection: EU summary of product characteristics. 2015. https://www.ema.europa.eu. Accessed 19 Feb 2019.

  58. European Medicines Agency. Taltz 80 mg solution for injection: EU summary of product characteristics. 2016. https://www.ema.europa.eu. Accessed 19 Feb 2019.

  59. European Medicines Agency. Kyntheum 210 mg solution for injection: EU summary of product characteristics. 2017. https://www.ema.europa.eu. Accessed 19 Feb 2019.

  60. European Medicines Agency. STELARA 45 and 90 mg solution for injection: EU summary of product characteristics. 2019. https://ec.europa.eu/health/documents/community-register/2009/2009011653548/anx_53548_en.pdf. Accessed 19 Feb 2019.

  61. Levin AA, Gottlieb AB. Specific targeting of interleukin-23p19 as effective treatment for psoriasis. J Am Acad Dermatol. 2014;70(3):555–61.

    Article  CAS  Google Scholar 

  62. Ergen EN, Yusuf N. Inhibition of interleukin-12 and/or interleukin-23 for the treatment of psoriasis: what is the evidence for an effect on malignancy? Exp Dermatol. 2018;27(7):737–47.

    Article  CAS  Google Scholar 

  63. Beck KM, Yang EJ, Sekhon S, et al. IL-23 inhibitors for psoriasis. Curr Dermatol Rep. 2018;7(2):119–24.

    Article  Google Scholar 

  64. Al-Salama ZT, Scott LJ. Guselkumab: A review in moderate to severe plaque psoriasis. Am J Clin Dermatol. 2018;19(6):907–18.

    Article  Google Scholar 

  65. Abbvie. AbbVie receives CHMP positive opinion for risankizumab (SKYRIZI™) for the treatment of moderate to severe plaque psoriasis [media release]. https://news.abbvie.com. Accessed 28 Feb 2019.

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

    Article  CAS  Google Scholar 

  67. Langley RG, Tsai TF, Flavin S, et al. Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double-blind, phase III NAVIGATE trial. Br J Dermatol. 2018;178(1):114–23.

    Article  CAS  Google Scholar 

  68. Lee EB, Amin M, Bhutani T, et al. Emerging therapies in psoriasis: a systematic review. Cutis. 2018;101(3S):5–9.

    PubMed  Google Scholar 

  69. Cui L, Chen R, Subedi S, et al. Efficacy and safety of biologics targeting IL-17 and IL-23 in the treatment of moderate-to-severe plaque psoriasis: a systematic review and meta-analysis of randomized controlled trials. Int Immunopharmacol. 2018;62:46–58.

    Article  CAS  Google Scholar 

  70. European Medicines Agency. Tremfya (guselkumab): EU assessment report. 2017. http://www.ema.europa.eu. Accessed 23 Jan 2018.

  71. Jia X, Zhao Y, Carrico J, et al. Cost-effectiveness of tildrakizumab in U.S. patients with moderate-to-severe plaque psoriasis [e-poster 8694]. In: AAD Annual Meeting. 2019.

  72. Nast A, Spuls PI, van der Kraaij G, et al. European S3-guideline on the systemic treatment of psoriasis vulgaris—update apremilast and secukinumab—EDF in cooperation with EADV and IPC. JEADV. 2017;31:1951–63.

    CAS  PubMed  Google Scholar 

  73. National Institute for Health and Care Excellence (NICE). Tildrakizumab for treating moderate to severe plaque psoriasis [ID1060]. 2019. https://www.nice.org.uk. Accessed 19 Mar 2019.

  74. National Institute for Health and Care Excellence (NICE). Guselkumab for treating moderate to severe plaque psoriasis. 2018. https://www.nice.org.uk. Accessed 23 Jan 2019.

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Acknowledgements

During the peer review process, the manufacturer of tildrakizumab was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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Correspondence to James E. Frampton.

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The preparation of this review was not supported by any external funding.

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James Frampton is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

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The manuscript was reviewed by:KM Beck, Department of Dermatology, University of California San Francisco, San Francisco, CA, USA, SK Dubey, Department of Pharmacy, Birla Institute of Technology & Science (BITS), Pilani, Rajasthan, India; M. Galluzzo, Department of Dermatology, University of Rome ‘Tor Vergata’, Rome, Italy; MJ Gooderham Department of Medicine, Queen’s University, Kingston, ON, Canada, L Puig, Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.

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Frampton, J.E. Tildrakizumab: A Review in Moderate-to-Severe Plaque Psoriasis. Am J Clin Dermatol 20, 295–306 (2019). https://doi.org/10.1007/s40257-019-00435-9

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