Frontline Forum Part 2: Topical Therapy for Corticosteroid-Responsive Dermatoses

Read part 1 here.

Read part 3 here.

Formulations and Epidermal Barrier Dysfunction

Turning to epidermal barrier dysfunction, Del Rosso pointed out that using betamethasone dipropionate spray, which he refers to as a “sprotion” because it is a lotion that is sprayed onto the skin, offers some interesting advantages. When looking at the vasoconstrictor assay for this formulation, for example, it turned out to be of medium potency, compared with betamethasone dipropionate augmented, which is super potent. However, Del Rosso presented efficacy data out to day 15 showing that these 2 agents do not differ in their efficacy despite one agent being graded as weaker based on the vasoconstrictor assay.

That is why the vasoconstrictor assay is a somewhat outdated measure, Stein Gold added. She said that she worries an augmented medication can easily pass into the dermis and constrict the deep vessels, which may lead to potential systemic concerns.

Stein Gold discussed the benefits of the spray lotion vehicle, which enables a drug depot effect. “It [the spray lotion vehicle] allows that drug to kind of sit for a little while within the epidermis and slowly transmit through the skin,” she explained. “And by doing that, we allow that drug to be around for a longer period of time. It’s not just traversing right through the skin and right into the systemic circulation, but hanging around for longer, depoting within the skin, so we don’t see the vasoconstriction so rapidly.”

She added, “We have the beauty of access to that drug over a long, nice period of time, a nice sustained effect on and increased effect on efficacy while minimizing the problems that we don’t want to see with a potent steroid.”

Del Rosso added that studies were conducted with different excipients for this spray lotion; the excipient that was chosen was found to be the one that allowed the most even distribution of the medication.

Del Rosso integrated the concept of epidermal barrier dysfunction with the importance of formulation and vehicle by highlighting the point that the skin has permeability barriers, antimicrobial barriers, immunological barriers, and ultraviolet light barriers. Barrier dysregulation and dysfunction are seen in both AD and psoriasis, involving not just lipids but structural proteins as well. Del Rosso shared data that good moisturization and gentle cleansing by patients with AD impacted the amount of medication needed as well as how much the disease might flare. Some formulations are able to interact with the barrier and barrier dysfunction in such a way that the medication becomes a reservoir and is slowly released, mitigating concerns with systemic absorption.

“With roflumilast [Zoryve cream], you get concerned about how much absorption you’re going to get, because if you absorb too much, you’re going to get the same kind of side effects you get with apremilast [Otezla]—the [gastrointestinal] side effect. But [patients] didn’t get it because it actually reservoirs the drug and then it slowly releases,” Del Rosso said. Given that transepidermal water loss increases during a flare of AD, Del Rosso offers an important pearl for clinicians when treating patients with AD by emphasizing good moisturization for these patients.

West agreed. “We’ve had many discussions over the years by many awesome thought leaders and physicians and providers that we don’t have to use a lot of therapeutic drugs if we moisturize and actually repair the barrier,” he said. “If we can address the barrier more readily and become more educated, then we may not even have to use as many of the therapies. Fixing that barrier makes a little bit of a difference—and maybe evena large difference.”

Chao added that when his patients taking isotretinoin use EpiCeram, he notices fewer eczematous eruptions on the face and improvement in the cheilitis, which patients taking isotretinoin frequently have.

Real World Cases and Treatment Pearls

To really understand the options, the panelists discussed a few patient cases. The first patient was a handyman with thick psoriatic plaques on his elbows and knees. The patient used intermittent topical therapy in the past with corticosteroids and calcipotriene and also has concerns about corticosteroid use and is wary about adverse effects. The patient achieved an excellent response with twice daily application of clobetasol 0.025% cream in an area that is traditionally difficult to treat, given the thickness of the dermis and lichenification of the skin. Given that this patient was a handyman, the panelists agreed that he would not want something that was greasy—he needed to be able to handle saws and hammers. He also would want something that is simple (ie, monotherapy), because he was constantly traveling. This case illustrated an excellent result with a cream-based vehicle with only 2 weeks of monotherapy with a lower concentration of steroids (the FDA label states the medication should be used consecutively only for up to 2 weeks).

Although some clinicians may doubt the efficacy of a cream-based vehicle with a lower concentration of steroids on elbows and knees, this case illustrated excellent results with twice daily application for 2 weeks. If the patient still had residual disease, some clinicians might recommend twice weekly application in the maintenance phase.

Regarding this case, West stated, “We should be picky with products these days.” He added that the goal should be to minimize the exposure to steroids while maximizing efficacy.

Del Rosso also presented a case of a woman with sun damage. The patient was a retired teacher who enjoyed golfing; she presented with sun-damaged skin and moderate to severe pruritus. She recently had been treated with over the counter creams (eg, salicylic acid, urea) and moisturizers; more remote therapies included topical corticosteroid ointments, calcipotriene, and etanercept. After 2 weeks, she had some, but not complete, improvement but she almost looked bruised.

“She needs another week or 2. Her skin color, her erythema, is still pretty significant,” Stein Gold said. “But for 2 weeks it’s a nice jump start. I don’t think she’s necessarily where she needs to be just yet.”

The panelists agreed that this patient needed more treatment. Del Rosso and Stein Gold added that although patients may improve on twice-daily treatment for 2 weeks, they still may require further therapy to clear their disease. Del Rosso suggested reducing the frequency, possibly to every other day.

Clinicians may have the misperception that all patients will be clear on 2 weeks of corticosteroids, but this is not the case, he explained. Stein Gold added that topical steroids often kick in faster than expected, but it may not be in those initial 2 weeks.