Solve the Challenges of Mild to Moderate Psoriasis

Evolving research on the pathogenesis and underlying causes of psoriasis doing more than fueling a robust pipeline; it is changing the way dermatologist assess individual patient needs and optimally manage their skin disease and quality of life (QOL). Linda Stein Gold, MD, detailed how best to use these advances to develop more effective, patient-centric treatment plans in her presentation at Maui Derm for Dermatologists 2022 held in Maui, Hawaii.¹

Previously, she noted, topical corticosteroids and nonsteroidal agents such as vitamin D used either as a monotherapy or combination therapy were main stays. They often served as first-line treatment and informed the scope of treatment modalities.

However, this generation of topical and oral treatments opens up more adaptable approaches, particularly for patients with mild to moderate psoriasis, said Stein Gold, who is director of clinical research and division head of the Department of Dermatology at Henry Ford Hospital in Detroit, Michigan. “A lot of patients [with mild to moderate disease] have given up on getting their psoriasis under control, and they need to demand more. We need treatment options that will allow for better efficacy and long-term disease control.”

“Contrary to popular belief, localized psoriasis is not easier to clear than more diffuse disease,” Stein Gold said. “In fact, localized psoriasis can be equally if not more challenging to treat [than diffuse disease] and very difficult to get under control. It is also important to keep in mind that even mild disease can have a profound impact on the patient’s quality of life.”

Research data supports that conclusion. She cited a 2016 study² comparing disease-associated cytokine expression in the skin between mild and severe psoriasis. Paradoxically, researchers found that mild psoriasis was characterized by higher numbers of T cells in skin lesions, higher interleukin (IL)-17A expression, and stronger expression of the core psoriasis transcriptome.

Results of 2021 study for which Stein Gold was lead author explored a new solution for combatting mild to moderate psoriasis.³ She and fellow researchers investigated the efficacy and safety of apremilast (Otezla; Amgen Inc) in a large cohort of patients with mild to moderate plaque psoriasis and found treatment to be effective with a safety consistent with the established safety profile of the medication.

According to Stein Gold, this novel oral phosphodiesterase 4 (PDE4) inhibitor may be a good option for patients with mild to moderate localized psoriasis. In her view, it could be particularly useful for long-term management.

New medications and formulations may also address unmet needs for areas that could be difficult to treat with traditional topical creams alone, especially scalp and nail psoriasis. Also in clinical trials are studies exploring combination therapies for apremilast and foam formulations that target plaque psoriasis.

Durability has been an ongoing therapeutic issue, Stein Gold said. Potent topical corticosteroids are a short-term solution to a long-term disease like psoriasis and as such, nonsteroidal treatment options would be more desirable, particularly for long-term treatment and management plans, she added.

Many clinicians report that nonsteroidal options do not work well in psoriasis cases, according to Stein Gold. In her experience, dermatologists have not had the nonsteroidal options that provided patients with sufficient levels of efficacy and tolerability—until now.

“The new nonsteroidal options such as tapinarof (Dermavant Sciences, Inc) and roflumilast (ARQ-151; Arcutis Biotherapeutics, Inc) give us efficacy and tolerability that we have not seen in the past,” she said. “The foam vehicle of roflumilast is a wonderful option for scalp psoriasis. Tapinarof gives some patients a durable remission that may allow them a drug holiday that lasts on average 4 months. Fortunately, the safety profile is also favorable, with the most common side effect being mild to moderate folliculitis occurring in about 20% of patients,” added Stein Gold.

Another misconception is that nonsteroidal options cause local skin irritation and tend to sting and burn. A well-tolerated topical medication is critical to enhancing patient adherence and, thereby, ultimately achieving the desired efficacy. The new topical PDE4 inhibitor roflumilast and the first-in-class nonsteroidal small molecule tapinarof (aryl hydrocarbon receptor agonist) could positively impact the treatment regimens of psoriasis patients particularly because of their excellent tolerability, Stein Gold said.

“The fact that we have good tolerability with both new options allows ease of use for sensitive areas including the face, skin folds and genital area,” she added.

These new nonsteroidal medications have not been studied yet in combination therapy. However, if they are FDA approved, Stein Gold said that they will very likely be used in combination with topical corticosteroids.

“We are very fortunate to have some great options in the pipeline that will help us to help our patients. I hope that we continue to see new molecules for topical therapy as this represents the majority of the medications that we prescribe,” Stein Gold said. “Developing new drugs is an expensive endeavor, as less than 10% of drugs that enter phase 1 ever get FDA approved.”

Disclosures:

Stein Gold is an investigator, advisor and/or speaker for AbbVie, Amgen Inc, Arcutis Biotherapeutics Inc, LEO Pharma, Ortho Biologics, Dermavant Sciences, Pfizer, Eli Lilly and Company, Novartis, UCB, and Bristol Myers Squibb.

References:

1. Stein Gold L, Strober B, Leonardi C, et al. Psoriasis update: 2022. Presented at Maui Derm for Dermatologists 2022. Held January 24-28, 2022, in Maui Hawaii and virtual.

2. Kim J, Bissonnette R, Lee J, Correa da Rosa J, et al. The spectrum of mild to severe psoriasis vulgaris is defined by a common activation of il-17 pathway genes, but with key differences in immune regulatory genes. J Invest Dermatol (2016) 136, 2173e2182; doi: 10.1016/j.jid.2016.04.032 Accessed January 21, 2022.

3. SteinGold L, Papp K, Pariser D, et al. Efficacy and safety of apremilast in patients with mild-to-moderate plaque psoriasis: Results of a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Am Acad Dermatol. 2022 Jan;86(1):77-85. doi:10.1016/j.jaad.2021.07.040. Epub 2021 July 31. Accessed January 21, 2022.