Roflumilast shows treatment potential for seborrheic dermatitis

In the phase III STRATUM* trial, the investigational PDE4** inhibitor roflumilast improved multiple symptoms of moderate-to-severe seborrheic dermatitis (SD).

“Topical therapies are the standard of care for SD treatment, but today’s options come with limitations, including side effects and the inability to use on both hair- and non-hair-bearing areas of the body,” said study lead author Dr Andrew Blauvelt from Oregon Medical Research Center, Portland, Oregon, US, at EADV 2022.

In in vitro assays, roflumilast showed greater affinity for PDE4 than two other PDE4 inhibitors – apremilast and crisaborole. [J Pharmacol Exp Ther 2016;358:413-422] “[P]otency in in vitro assays correlates with higher efficacy in the clinic,” said Blauvelt. “[Indeed, in our study,] roflumilast foam demonstrated strong efficacy across multiple endpoints.”

Participants were 457 individuals (mean age 42 years, 50 percent male, 6 percent Asian) with at least moderate SD (93 percent with IGA*** score of 3) and ≤20-percent body-surface area involvement. About 92 percent of patients had SD in the scalp. More than two-thirds reported facial involvement, while half had ear involvement. They were randomized 2:1 to either QD roflumilast foam 0.3% or a vehicle foam for 8 weeks. [EADV 2022, abstract 3531]

The study met its primary endpoint, with 80 percent of roflumilast recipients achieving IGA Success^# as opposed to 59 percent of those on the vehicle by week 8 (p<0.0001). Roflumilast prevailed over the vehicle as early as week 2 (43 percent vs 27 percent; p=0.0003) and continued through week 4 (73 percent vs 48 percent; p<0.0001).

Although the vehicle seemed beneficial, Blauvelt noted that the treatment effect was not big enough, as seen in the clear statistical differences at all three major timepoints vs the active drug.

More than 50 percent of roflumilast recipients achieved IGA Clear status; only 28 percent of those on the vehicle were completely clear by week 8 (p<0.0001). Again, the advantage of the active drug over the vehicle was seen as early as week 2 (16 percent vs 6 percent; p=0.0023).

More roflumilast vs vehicle recipients achieved scores of 0 for two other important endpoints – erythema (58 percent vs 33 percent; p<0.0001) and scaling (58 percent vs 38 percent; p=0.0001).

Looking at itch, more roflumilast than vehicle recipients achieved WI-NRS^## 4-point response (64 percent vs 42 percent; p=0.0002). “[This represented] a 4-point drop in the worst itch over the last 24 hours,” explained Blauvelt. There were also significant improvements at the 2- (33 percent vs 16 percent; p=0.0019) and 4-week (48 percent vs 30 percent; p=0.0014) assessments.

Rates of any treatment-related treatment-emergent adverse events (AEs) were low in both roflumilast and vehicle arms (2.6 percent vs 3.3 percent), as were the rates of any treatment-emergent serious AEs (0.3 percent vs 0.0 percent) and study discontinuation owing to AEs (0.7 percent vs 2 percent). “[Roflumilast] turned out to be very safe and did not seem to have any issues,” said Blauvelt.

Almost all patients in both arms reported no signs of irritation, as seen in the local tolerability evaluations.

Important nonsteroidal alternative

“We are excited to share these [data highlighting] the potential for roflumilast foam to treat multiple signs and symptoms of SD, including itch, redness, and scaling,” said Dr Patrick Burnett, Arcutis Chief Medical Officer, in a press release.

“Roflumilast foam continues to demonstrate strong efficacy with a safety and tolerability profile that, if approved, should provide an important new non-steroidal treatment option for chronic use anywhere on the body, including the scalp,” Burnett added.

“SD is a very common disease that when we did this trial, patients came in rapidly. They came out of the woodwork, they were desperate … I was very surprised to see how easy it was to recruit for this trial [and] how many people were suffering from SD,” shared Blauvelt. “I call this the ‘happy trial’ [as] every time I saw patients, they seemed happy … Many patients responded in this trial.”