Dermatology
Plaque Psoriasis
Updates on the Topical Therapy Landscape in Plaque Psoriasis
Many patients with plaque psoriasis are initially treated with topical therapy. For this disease, using topical therapies is common sense; they are convenient, can be applied directly to the area of pathology, and provide effective control for a broad spectrum of disease severity. Historically, topical therapy for plaque psoriasis meant corticosteroid therapy. Over at least the last half century, corticosteroids have become available in different vehicles (ie, ointments, creams, gels, foams, and solutions) and in a wide range of potencies. They are broadly covered by insurers, without significant out-of-pocket costs for patients, and they have been the backbone of plaque psoriasis treatment for many years.
Despite these options, a major challenge in treating plaque psoriasis has been a lack of innovation in terms of nonsteroidal topical options. Although topical corticosteroids can be effective as acute treatment, their chronic use is associated with a number of potential cutaneous and systemic adverse effects. Thus, there has been a desire for highly effective and safe nonsteroidal therapies for quite some time. This was one of the topics that was heavily covered at the 2025 Fall Clinical Dermatology Conference and at many other conferences this year.
We have seen a seismic shift in the dialogue around topical corticosteroids. This treatment class was once our first—and often only—choice for all patients with plaque psoriasis. Most dermatologists know that topical corticosteroids were not meant to be used forever, but we often did not have better topical alternatives. We now better appreciate that, in addition to cutaneous side effects such as striae, cutaneous atrophy, and dyspigmentation of the skin, long-term topical corticosteroid use can potentially be associated with similar side effects to those that are seen with systemic corticosteroid use. Topical corticosteroid withdrawal, a heterogeneous collection of clinical findings that goes by a number of distinct names, is also a potential complication. There has recently been a focus on identifying advanced targeted nonsteroidal therapies that offer efficacy that is on par with that of topical corticosteroids without the multitude of side effects associated with chronic use.
Two nonsteroidal agents that were discussed at the 2025 Fall Clinical Dermatology Conference during the session titled “The Changing Landscape of Topical Therapies” were tapinarof and roflumilast. As Bruce Strober, MD, highlighted during the session, while these are the most recently US Food and Drug Administration (FDA)–approved topical agents for plaque psoriasis, they have been on the market for a few years, which has given us incredible insight into the role they can play in routine clinical practice.
Tapinarof is an aryl hydrocarbon receptor (AhR) modulator. The AhR is a cellular sensor and nuclear receptor that is designed to detect perturbations in barrier homeostasis, making it an attractive target for chronic inflammatory skin diseases. Tapinarof leverages this pathway to help normalize dysregulation in cutaneous inflammation and barrier function. One particularly exciting finding highlighting the therapeutic potential for this target came from the PSOARING 3 trial, in which it was found that a sizable number of patients who achieved disease clearance on therapy were able to stop therapy for several months before the return of clinically significant skin lesions.
Roflumilast is an inhibitor of PDE4, an enzyme that is normally responsible for the breakdown of cyclic adenosine monophosphate. Inhibiting this enzyme can limit inflammation mediated by a broad array of T cells, including those highly relevant to psoriasis pathogenesis. Roflumilast is a highly targeted small molecule that has the ability to inhibit inflammation and normalize epidermal barrier disease. Roflumilast cream has an indication for the treatment of plaque psoriasis that includes intertriginous areas of the skin. This is compelling and significant because we have lacked agents with robust data and on-label indications for inverse psoriasis, which often involves sensitive skin where the use of a topical corticosteroid is limited. Roflumilast foam also has an indication for plaque psoriasis that includes the scalp, which is another challenging disease site where drug delivery and tolerability were previously limited with topical corticosteroids, especially across a diverse array of hair types.
Both tapinarof and roflumilast can be used from head to toe and are quite well tolerated, with a convenient once-daily application, limited systemic absorption, and an elegant cosmetic formulation, providing reassurance for both chronic and extensive use. In addition, both have well-documented safety across multiple clinical trials and indications, including atopic dermatitis (for tapinarof and roflumilast) and seborrheic dermatitis (for roflumilast). These 2 options have quickly become go-to treatments in the management of chronic plaque psoriasis.
Despite the rapid evolution and success that we have seen in the systemic treatment of plaque psoriasis, we will always need topical therapies to manage this condition. It is truly exciting to see a reinvestment in novel advanced topical therapies, and this innovation looks to continue over the coming decades.
Draelos ZD, Adam DN, Hong HCH, et al. Efficacy and safety of roflumilast cream for chronic plaque psoriasis with facial/neck and intertriginous area involvement: a post hoc analysis from a randomized controlled trial. Br J Dermatol. 2023;188(6):810-812. doi:10.1093/bjd/ljad060
Grossmann MC, Pixley JN, Feldman SR. A review of topical tapinarof for the treatment of plaque psoriasis. Ann Pharmacother. 2024;58(1):76-85. doi:10.1177/10600280231164775
Lebwohl MG, Kircik LH, Moore AY, et al. Effect of roflumilast cream vs vehicle cream on chronic plaque psoriasis: the DERMIS-1 and DERMIS-2 randomized clinical trials. JAMA. 2022;328(11):1073-1084. doi:10.1001/jama.2022.15632
Lebwohl MG, Stein Gold L, Strober B, et al. Phase 3 trials of tapinarof cream for plaque psoriasis. N Engl J Med. 2021;385(24):2219-2229. doi:10.1056/NEJMoa2103629
Lo A, Greenzaid JD, Gantz HY, Chodri K, Feldman SR. Clinical pharmacokinetics and pharmacodynamics of topical non-biological therapies for psoriasis patients. Expert Opin Drug Metab Toxicol. 2024;20(4):235-248. doi:10.1080/17425255.2024.2337749
Prieto K, Duong JQ, Feldman SR. Tapinarof cream for the topical treatment of plaque psoriasis in adults. Expert Rev Clin Immunol. 2024;20(4):327-337. doi:10.1080/1744666X.2023.2296607
Smith B, Collier MR, Wu JJ. Roflumilast cream vs vehicle cream and chronic plaque psoriasis. JAMA. 2023;329(7):594-595. doi:10.1001/jama.2022.22646
Stein Gold L, Adam DN, Albrecht L, et al. Long-term safety and effectiveness of roflumilast cream 0.3% in adults with chronic plaque psoriasis: a 52-week, phase 2, open-label trial. J Am Acad Dermatol. 2024;91(2):273-280. doi:10.1016/j.jaad.2024.03.030
Stein Gold LF, Frey C, Lio P, Strober B. The changing landscape of topical therapies. Session presented at: 2025 Fall Clinical Dermatology Conference; October 23-26, 2025; Las Vegas, NV.
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. J Am Acad Dermatol. 2022;87(4):800-806. doi:10.1016/j.jaad.2022.06.1171
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