Skip to main content
SpringerLink
Log in

New Topical Therapies for Psoriasis

  • Leading Article
  • Published:
American Journal of Clinical Dermatology Aims and scope Submit manuscript

A Correction to this article was published on 14 December 2021

This article has been updated

Abstract

Psoriasis is a chronic immune-mediated skin disease with a significant impact on patients’ quality of life. Mild-to-moderate forms of the disease usually require long-term topical treatment, but prolonged use of corticosteroids and vitamin D analogues is limited by adverse effects. With further understanding of psoriasis pathogenesis, new molecules are emerging aiming to fulfil these clinical needs. Tapinarof, an aryl hydrocarbon receptor modulator, has completed a phase III study and demonstrated good efficacy results, even in long treatment courses, with a favourable safety profile. It additionally appears to have a promising remitting effect as patients presented with an average relapsing time of over 3 months. Roflumilast, a phosphodiesterase type 4 inhibitor, also underwent a phase III study with significant lesion improvement and notable pruritus management, and with no reported side effects. Roflumilast was evaluated as an option for intertriginous areas with good outcomes in a small sample, but larger trials are required. The Janus kinase-signal transducer and activator of transcription pathway has been targeted in recent clinical investigations with promising options, currently with brepocitinib pending phase IIb results. Ongoing preclinical studies involving interleukin-2 inhibition, RNA modulators and amygdalin analogues may lead to forthcoming clinical trials. New topical drugs are successfully emerging and future research comparing them to classical options will dictate their clinical role in the treatment of psoriasis.

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

Similar content being viewed by others

Change history

References

  1. Armstrong AW, Read C. Pathophysiology, clinical presentation, and treatment of psoriasis: a review. JAMA. 2020;323(19):1945–60. https://doi.org/10.1001/jama.2020.4006.

    Article  CAS  PubMed  Google Scholar 

  2. Gerdes S, Körber A, Biermann M, Karnthaler C, Reinhardt M. Absolute and relative psoriasis area and severity index (PASI) treatment goals and their association with health-related quality of life. J Dermatolog Treat. 2020;31(5):470–5. https://doi.org/10.1080/09546634.2020.1746734.

    Article  PubMed  Google Scholar 

  3. González-Parra S, Daudén E. Psoriasis and depression: the role of inflammation. Actas Dermosifiliogr. 2019;110(1):12–9. https://doi.org/10.1016/j.ad.2018.05.009.

    Article  PubMed  Google Scholar 

  4. Dalgard FJ, Gieler U, Tomas-Aragones L, et al. The psychological burden of skin diseases: a cross-sectional multicenter study among dermatological out-patients in 13 European countries. J Invest Dermatol. 2015;135(4):984–91. https://doi.org/10.1038/jid.2014.530.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hawkes JE, Yan BY, Chan TC, Krueger JG. Discovery of the IL-23/IL-17 signaling pathway and the treatment of psoriasis. J Immunol. 2018;201(6):1605–13. https://doi.org/10.4049/jimmunol.1800013.

    Article  CAS  PubMed  Google Scholar 

  6. Girolomoni G, Strohal R, Puig L, Bachelez H, Barker J, Boehncke WH, et al. The role of IL-23 and the IL-23/TH17 immune axis in the pathogenesis and treatment of psoriasis. J Eur Acad Dermatol Venereol. 2017;31:1616–26. https://doi.org/10.1111/ijlh.12426.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bergboer JGM, Zeeuwen PLJM, Schalkwijk J. Genetics of psoriasis: evidence for epistatic interaction between skin barrier abnormalities and immune deviation. J Invest Dermatol. 2012;132(10):2320–31. https://doi.org/10.1038/jid.2012.167.

    Article  CAS  PubMed  Google Scholar 

  8. Gelfand JM, Gordon KB, Gottlieb A, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. J Am Acad Dermatol. 2009;60(4):643–59. https://doi.org/10.1016/j.jaad.2008.12.032.

    Article  PubMed  Google Scholar 

  9. Kaushik SB, Lebwohl MG. Psoriasis: which therapy for which patient: psoriasis comorbidities and preferred systemic agents. J Am Acad Dermatol. 2019;80(1):27–40. https://doi.org/10.1016/j.jaad.2018.06.057.

    Article  PubMed  Google Scholar 

  10. Kelly A, Ryan C. Genital psoriasis: impact on quality of life and treatment options. Am J Clin Dermatol. 2019. https://doi.org/10.1007/s40257-019-00447-5.

    Article  PubMed  Google Scholar 

  11. Merola JF, Qureshi A, Husni ME. Underdiagnosed and undertreated psoriasis: nuances of treating psoriasis affecting the scalp, face, intertriginous areas, genitals, hands, feet, and nails. Dermatol Ther. 2018;e12589:1–15. https://doi.org/10.1111/dth.12589.

    Article  Google Scholar 

  12. Griffiths CEM, Gold LS, Cambazard F, Lowson D, Møller A, Paul C. Greater improvement in quality of life outcomes in patients using fixed-combination calcipotriol plus betamethasone dipropionate aerosol foam versus gel: results from the PSO-ABLE study. Eur J Dermatol. 2018;28(3):356–63. https://doi.org/10.1684/ejd.2018.3302.

    Article  CAS  PubMed  Google Scholar 

  13. Paul C, Gold LS, Cambazard F, et al. Calcipotriol plus betamethasone dipropionate aerosol foam provides superior efficacy vs. gel in patients with psoriasis vulgaris: randomized, controlled PSO-ABLE study. J Eur Acad Dermatol Venereol. 2017;31(1):119–26. https://doi.org/10.1111/jdv.13859.

    Article  CAS  PubMed  Google Scholar 

  14. Kragballe K, Gjertsen BT, De Hoop D, Karlsmark T, van de Kerkhof PC, Larkö O, et al. Double-blind, right/left comparison of calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris. Lancet. 1991;337:193–6.

    Article  CAS  PubMed  Google Scholar 

  15. Soleymani T, Hung T, Soung J. The role of vitamin D in psoriasis: a review. Int J Dermatol. 2015;54(4):383–92. https://doi.org/10.1111/ijd.12790.

    Article  CAS  PubMed  Google Scholar 

  16. Selmer J, Vestbjerg B, Præstegaard M, Gold LS. Phase 3 trial demonstrates that MC2-01 cream has improved treatment efficacy compared to calcipotriene plus betamethasone dipropionate topical suspension in patients with mild to moderate psoriasis vulgaris. Skin J Cutan Med. 2020;4(5): s36. https://doi.org/10.25251/skin.4.supp.36.

    Article  Google Scholar 

  17. Koo J, Tyring S, Werschler WP, et al. Superior efficacy of calcipotriene and betamethasone dipropionate aerosol foam versus ointment in patients with psoriasis vulgaris: a randomized phase II study. J Dermatolog Treat. 2016;27(2):120–7. https://doi.org/10.3109/09546634.2015.1083935.

    Article  CAS  PubMed  Google Scholar 

  18. Gold LS, Lebwohl MG, Sugarman JL, et al. Safety and efficacy of a fixed combination of halobetasol and tazarotene in the treatment of moderate-to-severe plaque psoriasis: results of 2 phase 3 randomized controlled trials. J Am Acad Dermatol. 2018;79(2):287–93. https://doi.org/10.1016/j.jaad.2018.03.040.

    Article  CAS  PubMed  Google Scholar 

  19. Lebwohl MG, Stein Gold L, Papp K, et al. Long-term safety and efficacy of a fixed-combination halobetasol propionate 0.01%/tazarotene 0.045% lotion in moderate-to-severe plaque psoriasis: phase 3 open-label study. J Eur Acad Dermatol Venereol. 2021;35(5):1152–60. https://doi.org/10.1111/jdv.17113.

    Article  CAS  PubMed  Google Scholar 

  20. Boehncke W, Schön MP. Psoriasis. Lancet. 2015;386(9997):983–94. https://doi.org/10.1016/S0140-6736(14)61909-7.

    Article  CAS  PubMed  Google Scholar 

  21. Belichón I, Blanch C, Rivera R, Comellas M, Lizán L. Adherence, satisfaction and preferences for treatment in patients with psoriasis in the European Union: a systematic review of the literature. Patient Prefer Adherence. 2016;10:2357–67.

    Article  Google Scholar 

  22. Rendon A, Schäkel K. Psoriasis pathogenesis and treatment. Int J Mol Sci. 2019;20(6):1–28. https://doi.org/10.3390/ijms20061475.

    Article  CAS  Google Scholar 

  23. Bissonnette R, Stein Gold L, Rubenstein DS, Tallman AM, Armstrong A. Tapinarof in the treatment of psoriasis: a review of the unique mechanism of action of a novel therapeutic aryl hydrocarbon receptor-modulating agent. J Am Acad Dermatol. 2021;84(4):1059–67. https://doi.org/10.1016/j.jaad.2020.10.085.

    Article  CAS  PubMed  Google Scholar 

  24. Furue M, Hashimoto-hachiya A, Tsuji G. Aryl hydrocarbon receptor in atopic dermatitis and psoriasis. Int J Mol Sci. 2019;20(21):5424.

    Article  CAS  PubMed Central  Google Scholar 

  25. Smith SH, Jayawickreme C, Rickard DJ, et al. Tapinarof is a natural AhR agonist that resolves skin inflammation in mice and humans. J Invest Dermatol. 2017;137(10):2110–9. https://doi.org/10.1016/j.jid.2017.05.004.

    Article  CAS  PubMed  Google Scholar 

  26. Bissonnette R, Bolduc C, Maari C, et al. Efficacy and safety of topical WBI-1001 in patients with mild to moderate psoriasis: results from a randomized double-blind placebo-controlled, phase II trial. J Eur Acad Dermatol Venereol. 2012;26(12):1516–21. https://doi.org/10.1111/j.1468-3083.2011.04332.x.

    Article  CAS  PubMed  Google Scholar 

  27. Robbins K, Bissonnette R, Maeda-Chubachi T, et al. Phase 2, randomized dose-finding study of tapinarof (GSK2894512 cream) for the treatment of plaque psoriasis. J Am Acad Dermatol. 2019;80(3):714–21. https://doi.org/10.1016/j.jaad.2018.10.037.

    Article  CAS  PubMed  Google Scholar 

  28. Stein Gold L, Bhatia N, Tallman AM, Rubenstein DS. A phase 2b, randomized clinical trial of tapinarof cream for the treatment of plaque psoriasis: secondary efficacy and patient-reported outcomes. J Am Acad Dermatol. 2021;84(3):624–31. https://doi.org/10.1016/j.jaad.2020.04.181.

    Article  CAS  PubMed  Google Scholar 

  29. Stein Gold L, Strober B, Armstrong A, Hong HCH, Kircik L, Soung J, et al. Tapinarof cream 1% QD for the treatment of plaque psoriasis: efficacy and safety in two pivotal phase 3 trials. D3T03.3D, EADV Virtual, 29–31 October 2020. https://aad-eposters.s3.amazonaws.com/VMX2021/poster/25750/Tapinarof+Cream+1+Once+Daily+for+Plaque+Psoriasis+Secondary+Efficacy+Outcomes+from+Two+Pivotal+Phase+3+Trials.pdf. Accessed 22 Oct 2021.

  30. Lebwohl M, Stein Gold L, Strober B, Armstrong A, Hong HCH, Kircik L, et al. Tapinarof cream 1% QD for the treatment of plaque psoriasis: efficacy and safety in two pivotal phase 3 trials. Ski J Cutan Med. 2020;4(6): s75. https://doi.org/10.25251/skin.4.supp.75.

    Article  Google Scholar 

  31. Strober B, Gold LS, Bissonnette R, Armstrong A, Blauvelt A, Kircik L, et al. Tapinarof cream 1% once daily for plaque psoriasis: a long-term extension trial of a novel therapeutic aryl hydrocarbon receptor modulating agent [abstract 2860]. EADV 30th Congress; 2021.

  32. Cai L, Chen G, Lu Q, et al. A double-blind, randomized, placebo- and positive-controlled phase III trial of 1% benvitimod cream in mild-to-moderate plaque psoriasis. Chin Med J (Engl). 2020;133(24):2905–9. https://doi.org/10.1097/CM9.0000000000001221.

    Article  Google Scholar 

  33. Li H, Zuo J, Tang W. Phosphodiesterase-4 (PDE4) inhibitors for the treatment of inflammatory diseases. Front Pharmacol. 2018;9:1048. https://doi.org/10.3389/fphar.2018.01048.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lebwohl MG, Papp KA, Stein Gold L, et al. Trial of roflumilast cream for chronic plaque psoriasis. N Engl J Med. 2020;383(3):229–39. https://doi.org/10.1056/nejmoa2000073.

    Article  CAS  PubMed  Google Scholar 

  35. Torres T, Puig L. Apremilast: a novel oral treatment for psoriasis and psoriatic arthritis. Am J Clin Dermatol. 2018;19(1):23–32. https://doi.org/10.1007/s40257-017-0302-0.

    Article  PubMed  Google Scholar 

  36. Snape SD, Wigger-Alberti W, Goehring UM. A phase I randomized trial to assess the effect on skin infiltrate thickness and tolerability of topical phosphodiesterase inhibitors in the treatment of psoriasis vulgaris using a modified psoriasis plaque test. Br J Dermatol. 2016;175(3):479–86. https://doi.org/10.1111/bjd.14634.

    Article  CAS  PubMed  Google Scholar 

  37. Lebwohl M, Kircik LH, Moore A, Gold LS, Del Rosso J, Draelos ZD, et al. Once-daily roflumilast cream 0.3%, a potent phosphodiesterase-4 inhibitor, provided safe and effective treatment of psoriasis in the DERMIS-1 and DERMIS-2 phase 3 trials [abstract 2063]. EADV 30th Congress; 2021.

  38. Gooderham MJ, Alonso-Llamazares J, Bagel J, Brownigh JC, Draelos ZD, Grande KK, et al. Roflumilast cream 0.3% improved the severity and impact of itch in patients with chronic plaque psoriasis in the phase 3 DERMIS-1 and DERMIS-2 studies [abstract 146]. EADV 30th Congress; 2021.

  39. Hashim PW, Chima M, Kim HJ, et al. Crisaborole 2% ointment for the treatment of intertriginous, anogenital, and facial psoriasis: a double-blind, randomized, vehicle-controlled trial. J Am Acad Dermatol. 2020;82(2):360–5. https://doi.org/10.1016/j.jaad.2019.06.1288.

    Article  CAS  PubMed  Google Scholar 

  40. Rafael A, Torres T. Topical therapy for psoriasis: a promising future. Focus on JAK and phosphodiesterase-4 inhibitors. Eur J Dermatol. 2016;26(1):3–8. https://doi.org/10.1684/ejd.2015.2663.

    Article  CAS  PubMed  Google Scholar 

  41. Hsu L, Armstrong AW. JAK inhibitors: treatment efficacy and safety profile in patients with psoriasis. J Immunol Res. 2014;2014: 283617. https://doi.org/10.1155/2014/283617.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Nogueira M, Puig L, Torres T. JAK inhibitors for treatment of psoriasis: focus on selective TYK2 inhibitors. Drugs. 2020;80(4):341–52. https://doi.org/10.1007/s40265-020-01261-8.

    Article  CAS  PubMed  Google Scholar 

  43. Hosking AM, Juhasz M, Mesinkovska NA. Topical Janus kinase inhibitors: a review of applications in dermatology. J Am Acad Dermatol. 2018;79(3):535–44. https://doi.org/10.1016/j.jaad.2018.04.018.

    Article  CAS  PubMed  Google Scholar 

  44. Punwani N, Scherle P, Bsn RF, et al. Preliminary clinical activity of a topical JAK1/2 inhibitor in the treatment of psoriasis. J Am Dermatol. 2012;67(4):658–64. https://doi.org/10.1016/j.jaad.2011.12.018.

    Article  CAS  Google Scholar 

  45. Punwani N, Burn T, Scherle P, et al. Downmodulation of key inflammatory cell markers with a topical Janus kinase 1/2 inhibitor. Br J Dermatol. 2015;173:989–97. https://doi.org/10.1111/bjd.13994.

    Article  CAS  PubMed  Google Scholar 

  46. Papp KA, Menter MA, Abe M, et al. Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: results from two randomized, placebo-controlled, phase III trials. Br J Dermatol. 2015;173:949–61. https://doi.org/10.1111/bjd.14018.

    Article  CAS  PubMed  Google Scholar 

  47. Ports WC, Khan S, Lan S, et al. A randomized phase 2a efficacy and safety trial of the topical Janus kinase inhibitor tofacitinib in the treatment of chronic plaque psoriasis. Br J Dermatol. 2013;169(1):137–45. https://doi.org/10.1111/bjd.12266.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Papp KA, Bissonnette R, Gooderham M, et al. Treatment of plaque psoriasis with an ointment formulation of the Janus kinase inhibitor, tofacitinib: a phase 2b randomized clinical trial. BMC Dermatol. 2016;16(15):1–12. https://doi.org/10.1186/s12895-016-0051-4.

    Article  CAS  Google Scholar 

  49. Forman SB, Pariser DM, Poulin Y, et al. TYK2/JAK1 inhibitor PF-06700841 in patients with plaque psoriasis: phase IIa, randomized, double-blind, placebo-controlled trial. J Invest Dermatol. 2020;140(12):2359-70.e5. https://doi.org/10.1016/j.jid.2020.03.962.

    Article  CAS  PubMed  Google Scholar 

  50. Smith SH, Peredo CE, Takeda Y, et al. Development of a topical treatment for psoriasis targeting RORγ: from bench to skin. PLoS ONE. 2016;11(2):1–18. https://doi.org/10.1371/journal.pone.0147979.

    Article  CAS  Google Scholar 

  51. Ecoeur F, Weiss J, Kaupmann K, Hintermann S. Antagonizing retinoic acid-related-orphan receptor gamma activity blocks the T helper 17/interleukin-17 pathway leading to attenuated pro-inflammatory human keratinocyte and skin responses. Front Immunol. 2019;10:577. https://doi.org/10.3389/fimmu.2019.00577.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kang EG, Wu S, Gupta A, et al. A phase I randomized controlled trial to evaluate safety and clinical effect of topically applied GSK2981278 ointment in a psoriasis plaque test. Br J Dermatol. 2018;178(6):1427–9. https://doi.org/10.1111/bjd.16131.

    Article  CAS  PubMed  Google Scholar 

  53. Otake S, Otsubaki T, Uesato N, Ueda Y, Murayama T, Hayashi M. Topical application of BMS-509744, a selective inhibitor of interleukin-2-inducible T cell kinase, ameliorates imiquimod-induced skin inflammation in mice. Biol Pharm Bull. 2021;44(4):528–34. https://doi.org/10.1248/bpb.b20-00850.

    Article  CAS  PubMed  Google Scholar 

  54. Guo S, Zhang W, Weia C, et al. Serum and skin levels of miR-369-3p in patients with psoriasis and their correlation with disease severity. Eur J Dermatol. 2013;23(5):608–13. https://doi.org/10.1684/ejd.2013.2148.

    Article  CAS  PubMed  Google Scholar 

  55. Zhang W, Yi X, An Y, et al. MicroRNA-17-92 cluster promotes the proliferation and the chemokine production of keratinocytes: implication for the pathogenesis of psoriasis. Cell Death Dis. 2018;9:5. https://doi.org/10.1038/s41419-018-0621-y.

    Article  CAS  Google Scholar 

  56. Pradyuth S, Rapalli VK, Gorantla S, Waghule T, Dubey SK, Singhvi G. Insightful exploring of microRNAs in psoriasis and its targeted topical delivery. Dermatol Ther. 2020;33(6):1–9. https://doi.org/10.1111/dth.14221.

    Article  CAS  Google Scholar 

  57. Wu R, Zeng J, Yuan J, et al. MicroRNA-210 overexpression promotes psoriasis-like inflammation by inducing Th1 and Th17 cell differentiation. J Clin Invest. 2018;128(6):2551–68. https://doi.org/10.1172/JCI97426.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Feng H, Wu R, Zhang S, et al. Topical administration of nanocarrier miRNA-210 antisense ameliorates imiquimod-induced psoriasis-like dermatitis in mice. J Dermatol. 2020;47(2):147–54. https://doi.org/10.1111/1346-8138.1514.9.

    Article  CAS  PubMed  Google Scholar 

  59. Volpe E, Pattarini L, Martinez-Cingolani C, Meller S. Thymic stromal lymphopoietin links keratinocytes and dendritic cell-derived IL-23 in patients with psoriasis. J Allergy Clin Immunol. 2014;134(2):373-81.e4. https://doi.org/10.1016/j.jaci.2014.04.022.

    Article  CAS  PubMed  Google Scholar 

  60. López NG, Lagunas C, Juan A, Erwin JP. Topical application of an amygdalin analogue reduces inflammation and keratinocyte proliferation in a psoriasis mouse model. Exp Dermatol. 2020. https://doi.org/10.1111/exd.14390.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Dermatology, Centro Hospitalar Universitário do Porto, Centro Hospitalar do Porto, Edifício das Consultas Externas, Ex. CICAP, Rua D. Manuel II, s/n, 4100, Porto, Portugal

    Ana Maria Lé & Tiago Torres

  2. Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal

    Tiago Torres

Authors
  1. Ana Maria Lé
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tiago Torres
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tiago Torres.

Ethics declarations

Funding

No funding has been received for the preparation of this article.

Conflicts of interest

Ana Maria Lé has no conflicts of interest to declare. Tiago Torres declares the following conflicts of interest: AbbVie, Almirall, Amgen, Arena Pharmaceuticals, Biocad, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Fresenius Kabi, Janssen, LEO Pharma, Eli Lilly, MSD, Mylan, Novartis, Pfizer, Samsung-Bioepis, Sanofi-Genzyme, Sandoz and UCB.

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

AL and TT had the idea for the article, performed the literature search and data analysis, and drafted and critically revised the work.

Additional information

The original online version of this article was revised: The original version was revised due to update in article text

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lé, A.M., Torres, T. New Topical Therapies for Psoriasis. Am J Clin Dermatol 23, 13–24 (2022). https://doi.org/10.1007/s40257-021-00649-w

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40257-021-00649-w

Search

Navigation