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Topical Therapies for Psoriasis: Where do we start, and what's new?

Updated: 15 hours ago

By Zach Krauss, PharmD Candidate 2023; Juanita A. Draime, PharmD


Introduction

Psoriasis vulgaris is an inflammatory skin condition that has been estimated to affect ~2% of the general population of the world.(1) In recent years, there has been much development in the realm of systemic and biologic therapies for moderate-to-severe psoriasis which has revolutionized the treatment paradigm for the disease because full recovery/remission from psoriasis is attainable with these new therapy options. However, as clinicians, it’s important to be able to recognize the value of first-line therapies for any disease state, especially for lower acuity patients who most likely would prefer a less systemic option if possible. This review will cover the various available therapies for topical management of psoriasis while also discussing the newest addition to the roster for psoriasis treatment, topinarof.


Overview of Guideline Recommendations

The 2020 Joint AAD-NPF guidelines for treatment of psoriasis with topical/alternative medicine currently provides a schema for topical treatment of psoriasis with a list of approved medications outside of the biologic and systemic therapy space.(2) Classes outlined by the current guidelines include topical corticosteroids, calcineurin inhibitors, vitamin D analogues, tazarotene, moisturizers, salicylic acid, anthralin, and coal tar. Severity of psoriasis is determined most commonly by assessment of body surface area (BSA) covered by symptomatic lesions. <3%, 3-10%, and >10% are usually considered as mild, moderate, and severe psoriasis respectively, however, the guidelines recommend all topical agents as appropriate from mild through severe disease.


Topical Corticosteroids

One of the most commonly utilized groups of topical treatments, the topical corticosteroids, are often considered the true first-line when it comes to psoriasis management. This is partially due to their wide availability, multiple treatment formulations, and their moderate adverse effect profile which allows for utility in many populations. Table 1 outlines the generally accepted strength classes of topical corticosteroids based on vasoconstriction activity and overall efficacy. In patients with moderate-to-severe presentations of psoriasis, groups 1-3 are usually recommended as high-potency agents are likely necessary in order to impact symptoms.


Topical corticosteroids are sometimes considered potentially damaging to sensitive skin, specifically skin around the face or forearms.(3) Use is often limited to 4 weeks at a time in order to prevent unnecessary adverse effects. After a 4 week trial, utility/benefit should be reevaluated.


Table 1: Classification of Topical Corticosteroids(2)


Calcineurin Inhibitors

Topical calcineurin inhibitors block phosphorylation through their activity and in turn prevent the synthesis of proinflammatory cytokines by immune cells in dermal tissues. These agents are often recommended for use in patients with symptoms on thinner skin that might sometimes be too sensitive for use of topical corticosteroids. Studies have shown utility in the psoriasis patient population despite available calcineurin inhibitors lacking FDA approval for this indication.(4)


Vitamin D Analogues

This class of medications includes calcipotriene and calcitriol, which specifically have been shown to have impact in moderate psoriasis.(5) The adverse effect profile of vitamin D analogues is very limited and adverse reactions are usually only encountered in patients treating more than 30% body surface area at a time.(6) Of note, ultraviolet A light waves can decrease effectiveness of these analogues, so use in patients with history of phototherapy treatment might be disadvantageous.(7)


Tazarotene

Tazarotene is an FDA-approved psoriasis treatment which functions as a topical retinoid. Use based on clinical trials is usually for 8-12 weeks, and is recommended for mild-to-moderate symptomatic patients.(8,9) These trials showcased that tazarotene has specific added benefit, apparently, in patients experiencing palmar-plantar psoriasis or psoriasis involvement with the nails. Tazarotene has been showcased to be very effective for treatment when combined with topical corticosteroids as well, creating a place in therapy for this as a second-line adjunctive agent.(10) Tazarotene should not be used with pregnant patients.


Moisturizers

Non-medicated moisturizers such as ointments, creams, lotions, and gels are all recommended as nonpharmacologic management agents for psoriasis. The risk of adverse reactions with these agents is very limited, and most moisturizers can be safely reapplied multiple times daily, creating potential benefit for patients who otherwise lose benefit from their other topical treatments over the course of the day.(11)


Salicylic Acid, Anthralin, and Coal Tar

Salicylic has potential benefit in psoriasis patients because of its potential to be a keratolytic agent on the skin. Salycylic has been shown in clinical trials to be effective both as a single agent and also as a combination treatment option and is fairly safe when used in recommended doses.(12,13)


Anthralin or dithranol is another agent that can be used topically that has showcased benefits assumed to be a result of the prevention of keratinocyte differentiation in skin tissues.(14) Anthralin should not be used on the face, and has the potential to stain skin, so should be used carefully on other visible areas of the skin.


Coal tar/LCD [liquor carbonis detergens] is another potential topical agent that has been postulated to create impact by suppressing DNA synthesis in keratinocytes while also affecting immunologic functioning. There have been some animal studies showcasing fetal toxicity. Coal tar formulations are usually accompanied by a strong tar odor, which creates difficulty with ensuring adherence in many patients.(15)


Emerging Therapy Options: Topinarof and Roflumilast

In May of 2022, the FDA approved Vtama (tapinarof) for the treatment of psoriasis in adults. It has the first novel mechanism approved for this indication in many years. Tapinarof acts as an aryl hydrocarbon receptor agonist and is indicated to be used once daily.(16) This mechanism is novel and its direct action within psoriasis is posited to be related to downregulation of downstream proinflammatory cytokines such as IL-17.

Its approval was promptly followed by the approval of Zoryve (roflumilast), which is a PDE-4 inhibitor also indicated for treatment of psoriasis once daily as a topical treatment. Roflumilast’s oral formulation is approved as a treatment for COPD/Asthma.


Clinical Trials Data

A total of 1025 patients with persistent plaque psoriasis affecting 3 to 20% of the total body surface area were randomly assigned in a 2:1 ratio to either tapinarof 1% cream or vehicle used once daily in two similar phase III trials (PSOARING 1 and PSOARING 2). Patients in the tapinarof groups were more likely than those in the placebo group to reach the primary goal of a Physician Global Assessment (PGA) score of 0 (clear) or 1 (nearly clear) at week 12 and at least a two-point decline in the PGA scale (35.4 versus 6 percent [adjusted difference 29.(4) percentage points; RR 5.8, 95% CI 2.9-11.5] in PSOARING 1 and 40.2 versus 6.3 percent [adjusted difference 33.9 percentage points; RR 6.1, 95% CI 3.3-11.4] in PSOARING 2). The tapinarof groups outperformed the vehicle groups in terms of improvements in the psoriasis area and severity index (PASI 75 and PASI 90, respectively).(17) Long term safety/efficacy was established in the PSOARING 3 LTE study.(18)


Two randomized controlled trials for roflumilast, DERMIS-1 and 2, were carried out in a total of 881 subjects with mild to severe plaque psoriasis. Randomization of 2:1 for treatment to placebo was carried out for 8 weeks. In DERMIS-1 the difference using the I-IGA scale was 39.7% (41.5% vs. 5.8%, 95% CI 32.4% - 47.0%) and in DERMIS-2, the change was 29.5% (36.7% vs. 7.1%, 95% CI 21.5% - 37.6%).(19)


Conclusion

This article summarizes the currently available treatment options for topical management of psoriasis while also highlighting tapinirof and roflumilast, which are novel agents indicated for the treatment of psoriasis. These new agents are not included in the AAD/NPF psoriasis guidelines, but it is likely that the novel treatment approach and fairly strong clinical data will integrate both into clinical practice as an alternative first-line option, especially for patients who might otherwise not wish to continue therapy with topical corticosteroids.


Table 2: Available classes of agents, pros and cons of use, and place in therapy(20)

 

1. Parisi R, Iskandar IYK, Kontopantelis E, et al. National, regional, and worldwide epidemiology of psoriasis: systematic analysis and modelling study. BMJ. 2020;369:m1590. Published 2020 May 28. doi:10.1136/bmj.m1590.

2. Elmets CA, Korman NJ, Prater EF, et al. Joint AAD-NPF Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures. J Am Acad Dermatol. 2021;84(2):432-470. doi:10.1016/j.jaad.2020.07.087

3. Abraham A, Roga G. Topical steroid-damaged skin. Indian J Dermatol. 2014;59(5):456-459. doi:10.4103/0019-5154.139872.

4. Gribetz C, Ling M, Lebwohl M, et al. Pimecrolimus cream 1% in the treatment of intertriginous psoriasis: a double-blind, randomized study. J Am Acad Dermatol. 2004;51(5):731-738. doi:10.1016/j.jaad.2004.06.010.

5. Highton A, Quell J. Calcipotriene ointment 0.005% for psoriasis: a safety and efficacy study. Calcipotriene Study Group. J Am Acad Dermatol. 1995;32(1):67-72. doi:10.1016/0190-9622(95)90186-8.

6. Scott LJ, Dunn CJ, Goa KL. Calcipotriol ointment. A review of its use in the management of psoriasis. Am J Clin Dermatol. 2001;2(2):95-120. doi:10.2165/00128071-200102020-00008.

7. Lebwohl M, Hecker D, Martinez J, Sapadin A, Patel B. Interactions between calcipotriene and ultraviolet light. J Am Acad Dermatol. 1997;37(1):93-95. doi:10.1016/s0190-9622(97)70217-2

8. Tanghetti E, Lebwohl M, Stein Gold L. Tazarotene Revisited: Safety and Efficacy in Plaque Psoriasis and Its Emerging Role in Treatment Strategy. J Drugs Dermatol. 2018;17(12):1280-1287.

9. Lebwohl M, Ast E, Callen JP, et al. Once-daily tazarotene gel versus twice-daily fluocinonide cream in the treatment of plaque psoriasis. J Am Acad Dermatol. 1998;38(5 Pt 1):705-711. doi:10.1016/s0190-9622(98)70594-8.

10. Sugarman JL, Gold LS, Lebwohl MG, Pariser DM, Alexander BJ, Pillai R. A Phase 2, Multicenter, Double-Blind, Randomized, Vehicle Controlled Clinical Study to Assess the Safety and Efficacy of a Halobetasol/Tazarotene Fixed Combination in the Treatment of Plaque Psoriasis. J Drugs Dermatol. 2017;16(3):197-204.

11. Seite S, Khemis A, Rougier A, Ortonne JP. Emollient for maintenance therapy after topical corticotherapy in mild psoriasis. Exp Dermatol. 2009;18(12):1076-1078.

12. Lebwohl M. The role of salicylic acid in the treatment of psoriasis. Int J Dermatol. 1999;38(1):16-24.122.

13. Akamine KL, Gustafson CJ, Yentzer BA, et al. A double-blind, randomized clinical trial of 20% alpha/poly hydroxy acid cream to reduce scaling of lesions associated with moderate, chronic plaque psoriasis. J Drugs Dermatol. 2013;12(8):855-859.

14. de Korte J, van der Valk PG, Sprangers MA, et al. A comparison of twice-daily calcipotriol ointment with once daily short-contact dithranol cream therapy: quality-of-life outcomes of a randomized controlled trial of supervised treatment of psoriasis in a day-care setting. Br J Dermatol. 2008;158(2):375-381.

15. Alora-Palli MB, Perkins AC, Van Cott A, Kimball AB. Efficacy and tolerability of a cosmetically acceptable coal tar solution in the treatment of moderate plaque psoriasis: a controlled comparison with calcipotriene (calcipotriol) cream. Am J Clin Dermatol. 2010;11(4):275-283.

16. Product Information: VTAMA(R) topical cream, tapinarof topical cream. Dermavant Sciences Inc (per FDA), Long Beach, CA, 2022.

17. Lebwohl MG, Stein Gold L, Strober B, et al. Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis. N Engl J Med 2021; 385:2219.

18. Strober B, Stein Gold L, Bissonnette R, et al. One-year safety and efficacy of tapinarof cream for the treatment of plaque psoriasis: Results from the PSOARING 3 trial [published online ahead of print, 2022 Jun 27]. J Am Acad Dermatol. 2022;S0190-9622(22)02219-8. doi:10.1016/j.jaad.2022.06.1171.

19. Lebwohl M, Kircik LH, Moore AY, 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. Poster presented at the fall Clinical Dermatology Conference in Las Vegas, NV in October 2021.

20. National Psoriasis Foundation. Non-Steroidal Topical Treatments. Updated July 29, 2022. https://www.psoriasis.org/non-steroidal/. Accessed August 15, 2022.

 

Zach Krauss

PharmD Candidate 2023

Cedarville University






 


Juanita A. Draime, PharmD

Assistant Professor of Pharmacy Practice

Cedarville University





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