The results of two phase 3 clinical trials suggest a topical psoriasis treatment option.
Roflumilast cream demonstrated efficacy in patients with plaque psoriasis after 8 weeks of use, research shows.
Although known for its use treating chronic obstructive pulmonary disease, roflumilast was assessed in 2 clinical trials as a topical treatment of plaque psoriasis. It is a phosphodiesterase 4 (PDE4) inhibitor that is both potent and selective.
Both the efficacy and safety of topical roflumilast cream as a treatment for plaque psoriasis were examined in two phase 3 trials. The research team in both trials was led by Mark G. Lebwohl, MD, and Leon H. Kircik, MD, from the Icahn School of Medicine at Mount Sinai in New York.
“Treating psoriasis in intertriginous areas can be difficult because the skin in intertriginous areas is thinner and more sensitive, provides greater drug absorption, and is prone to adverse effects associated with topical therapies,” Lebwohl and colleagues wrote. “Results reported herein indicate that roflumilast may be an effective therapy for these difficult-to-treat areas.”
The 2 clinical trials—DERMIS-1 and DERMIS-2—were parallel-group, double-blind, and vehicle-controlled studies, with a combined total of 881 recruited participants. Those recruited for the studies were required to be 2 years of age or older and a clinical plaque psoriasis diagnosis for 6 months prior. Children needed a diagnosis only 3 months prior.
The investigators required those patients with psoriasis on the extremities, trunk, face, and/or intertriginous areas to have plaque psoriasis affecting between 2 - 20% of body surface area excluding palms, scalp, and foot soles, in order to be included. At minimum, the Investigator Global Assessment (IGA) rating was required to be mild for participation to be permitted.
The researcher team randomized eligible participants 2 to 1 to roflumilast cream, 0.3%, or vehicle cream once-per-day. All of those involved, including patients, clinical staff, investigators, and sponsors were unaware of individual treatments.
The investigators set the primary efficacy endpoint at patients receiving a rating of clear or almost clear on the IGA scale, as well as 2-grade improvement from baseline by the end of the trial’s 8 weeks. They had 9 secondary endpoints, including intertriginous IGA rating success, Worst Itch Numeric Rating Scale (WI-NRS) score, and a reduction in Psoriasis Area and Severity Index (PASI) score.
By the 8 week mark in DERMIS-1, the investigators found 108 participants (42.4%) treated with roflumilast reached the primary endpoint, compared with 8 participants (6.1%) of patients treated with the vehicle (difference, 39.6%; 95% CI, 32.3 - 46.9%; P = .001). By 8 weeks in DERMIS-2, they found 99 participants (37.5%) treated with roflumilast reached the primary endpoint compared with 9 participants (6.9%) in the vehicle arm (difference 28.8%;, 95% CI, 20.8 - 36.9%; P = .001).
The investigators, overall, saw statistically significant percentages in IGA success by 8 weeks in the treatment arms of both trials over the control groups. They found that of the 9 secondary endpoints, statistically significant differences favoring roflumilast compared with vehicle treatment were reported in both trials, including intertriginous IGA success, PASI score, and WI-NRS success.
Additionally, they found that topically administered roflumilast resulted in lower adverse effect rates than those of oral PDE4 inhibitors. The investigators found that 17 of the 18 participants in the treatment group for both trials, who reported diarrhea as an AE, reported mild cases. The majority of AE cases were reported in the beginning 2 week period of treatment and left after continued dosing.
The investigators added that these results indicate roflumilast may be more effective for intertriginous skin treatment, given that topical therapies typically have a harder time treating psoriasis in these areas due to the skin being thinner and more sensitive.
“In the current randomized clinical trials, few 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,” they wrote.
While the investigators state that further research will be needed to examine long-term safety and efficacy relative to alternative treatments, the results of both trials indicate positive findings for the treatment’s potential use for plaque psoriasis.
The study, “Effect of Roflumilast Cream vs Vehicle Cream on Chronic Plaque Psoriasis - The DERMIS-1 and DERMIS-2 Randomized Clinical Trials,” was published online by JAMA.