Psoriasis cream scores high in DERMIS trials

Applying roflumilast cream topically once-a-day helps clear plaque psoriasis in 8 weeks, according to pooled data from the phase III DERMIS-1 and DERMIS-2 trials.

Among 881 patients (mean age 47.5 years, 36.3 percent female) with chronic plaque psoriasis, eight weeks of treatment with roflumilast cream 0.3% vs the vehicle cream significantly increased the likelihood of achieving the primary efficacy endpoint of Investigator Global Assessment (IGA) success at the 8-week follow-up.

Specifically, IGA success was documented in 42.4 percent of patients with roflumilast and 6.1 percent with the vehicle in DERMIS-1 (difference, 39.6 percent, 95 percent confidence interval [CI], 32.3–46.9; p<0.001). The corresponding proportions in DERMIS-2 were 37.5 percent and 6.9 percent (difference, 28.9 percent, 95 percent CI, 20.8–36.9; p<0.001). IGA success was defined as achievement of clear or almost clear status plus a ≥2-grade improvement from baseline (score range, 0-4) at week 8. [JAMA 2022;328:1073-1084]

The same was true for secondary endpoints, with statistically significant differences favouring roflumilast vs vehicle seen in eight out of nine endpoints in DERMIS-1 and in all nine endpoints in DERMIS-2.

Some of these endpoints were intertriginous IGA success (difference, 66.5 percent in trial 1 and 51.6 percent in trial 2; p<0.001 for both), 75-percent reduction in Psoriasis Area and Severity Index (PASI) score (difference, 36.1 percent in trial 1 and 32.4 percent in trial 2; p<0.001 for both), and Worst Itch Numeric Rating Scale (WI-NRS) success at week 8 (four-point reduction on a scale of 0 [no itch] to 10 [worst imaginable itch]; difference, 42.6 percent in trial 1 and 30.2 percent in trial 2; p<0.001 for both).

“[F]ew stinging, burning, or application site reactions were reported with either roflumilast or vehicle, including among the subpopulation who used roflumilast in intertriginous areas, consistent with prior studies of topical roflumilast in psoriasis and atopic dermatitis,” the investigators said. [J Drugs Dermatol 2020;19:734-740; N Engl J Med 2020;383:229-239]

Treatment-emergent adverse events frequency was 25.2 percent with roflumilast vs 23.5 percent with vehicle in trial 1 and 25.9 percent vs 18.4 percent in trial 2. The frequency of serious adverse events was low at 0.7 percent vs 0.7 percent in trial 1 and 0 percent vs 0.7 percent in trial 2.

A boon for psoriasis in difficult-to-treat areas

A selective, highly potent phosphodiesterase 4 (PDE4) inhibitor, roflumilast in topical formulation is being evaluated for the treatment of several dermatologic conditions, including psoriasis (recently approved for plaque psoriasis by the US Food and Drug Administration), atopic dermatitis, and seborrheic dermatitis. [J Drugs Dermatol 2020;19:734-740; N Engl J Med 2020;383:229-239]

According to the American Academy of Dermatology/National Psoriasis Foundation guidelines for plaque psoriasis, most patients benefit from topical options. The first-line topical treatments include corticosteroids, vitamin D analogues, and retinoids (ie, tazarotene). [J Am Acad Dermatol 2021;84:432-470]

“However, topical corticosteroids have adverse effects with long-term use and limitations associated with facial or intertriginous application. Vitamin D analogues and retinoids may be used long-term but may cause irritation and have lower efficacy than topical corticosteroids, so they are commonly prescribed in combination with topical corticosteroids,” the investigators said.

In light of the efficacy results, the investigators believe that roflumilast will prove useful in the treatment of plaque psoriasis, particularly in intertriginous areas.

“Treating psoriasis in intertriginous areas can be difficult because the skin in [these] areas is thinner and more sensitive, provides greater drug absorption, and is prone to adverse effects associated with topical therapies. [Furthermore], intertriginous psoriasis may be resistant to topical medications, likely because of mechanical effects including friction,” they pointed out. [Reumatologia 2018;56:392-398; J Drugs Dermatol 2017;16:760-766; Expert Opin Pharmacother 2018;19:561-575]

Nevertheless, the efficacy of roflumilast relative to current tropical treatments for chronic plaque psoriasis remains unknown. The investigators called for further research to address this gap, as well as to assess the drug’s longer-term efficacy and safety.