Roflumilast Foam for Psoriasis: Efficacy, Tolerability, and Clinical Relevance

Topical treatment of plaque psoriasis can be difficult, especially on the scalp, where the use of creams or ointments is often hindered by the presence of hair. Adherence to available therapeutic options is frequently undermined by cosmetic incompatibility and application difficulties.

However, roflumilast foam, 0.3 percent, was engineered to address these limitations, offering a non-alcoholic, high-water-content vehicle designed for both scalp and body application. To investigate this formula, the ARRECTOR Phase 3 trial tested it in a diverse cohort across North America, targeting moderate-to-severe scalp psoriasis with concurrent mild-to-moderate nonscalp involvement.

Here's a look at the trial and its results, which were published in JAMA Dermatology in May 2025.

Study Design and Patient Profile

The double-blind, vehicle-controlled trial enrolled 432 participants aged 12 and older, randomized in a 2:1 ratio to receive either roflumilast foam or vehicle daily for eight weeks.

The inclusion criteria focused on patients with at least 10 percent scalp involvement and up to 20 percent nonscalp involvement, with moderate baseline severity on the Scalp–Investigator Global Assessment (S-IGA) and mild on the Body-IGA (B-IGA). Baseline demographics showed balanced distribution between arms, with a mean age of 47.3 years and a majority presenting Fitzpatrick skin types I–III. A history of topical corticosteroid use was reported by over 80 percent of participants.

Efficacy Outcomes: Investigator and Patient Perspectives

Looking at the results, roflumilast foam demonstrated statistically significant efficacy across all primary and secondary endpoints. By week eight, 66.4 percent of the roflumilast group achieved S-IGA success compared to 27.8 percent in the vehicle group, with a similar superiority in B-IGA success (45.5 percent versus 20.1 percent). Notably, improvements were observed early, with significant differences emerging by week two in both S-IGA and pruritus-related measures.

Patient-reported outcomes on the Scalp Itch-Numeric Rating Scale (SI-NRS) and Worst Itch-Numeric Rating Scale (WI-NRS) aligned with clinician assessments. A four-point improvement in scalp itch was reported by 65.3 percent of the roflumilast group by week eight versus 30.3 percent in the control arm. Importantly, significant pruritus reduction was documented as early as 24 hours post-application (mean change: –0.44 vs –0.09; P < .02), suggesting rapid onset of symptom relief. These early gains persisted and amplified through week eight across all itch metrics.

Functional and Symptom-Based Endpoints

Composite scores from the Psoriasis Symptoms Diary (PSD), which includes domains of itching, scaling, and pain, also showed superior improvement in the roflumilast arm. At week eight, 31.7 percent of roflumilast-treated patients reported no scalp itching, compared with 10.0 percent in the vehicle group. Scaling resolution was similarly higher (41.5 percent versus 13.6 percent), reinforcing the formulation’s efficacy in addressing visible and tactile disease components.

Further, 70.9 percent of the roflumilast group reached PSSI-75, and 50.1 percent achieved PASI-75, benchmarks commonly used to evaluate therapeutic impact.

Safety and Tolerability Profile

Adverse event (AE) rates were low in both study arms, with 26.7 percent of the roflumilast group and 16.6 percent of the vehicle group reporting any treatment-emergent AE. The vast majority were mild or moderate in severity, and only 1.8 percent in the roflumilast group discontinued due to AEs. Serious adverse events occurred in just 0.7 percent of patients in each arm, none of which were definitively linked to the study drug.

Local tolerability, assessed by both investigators and patients, was favorable across the board. Over 99 percent of investigator assessments and more than 94 percent of patient reports indicated no or only mild irritation at all time points. No signals emerged related to psychiatric symptoms, including depression or suicidal ideation, based on standardized instruments administered at each visit.

Implications for Clinical Practice

The foam’s composition—free from ethanol, propylene glycol, and known sensitizers—contributes to its favorable tolerability. Unlike many existing topicals, roflumilast foam accommodates application on both hair-bearing and non–hair-bearing areas. This versatility may simplify regimens for patients with multi-regional disease involvement, reducing the need for polypharmacy and potentially improving adherence.

Prior trials of roflumilast cream (such as DERMIS-1 and DERMIS-2) had shown comparable efficacy for nonscalp areas. However, this trial establishes that the foam vehicle achieves similar results while overcoming the practical limitations of creams in scalp application. While the study lacked an active comparator and was limited to eight weeks, the consistency across endpoints and alignment with earlier phase 2 data support the formulation’s clinical utility.

As a once-daily monotherapy compatible with scalp and body use, roflumilast offers a streamlined option for patients and clinicians seeking topical alternatives to corticosteroids in chronic plaque psoriasis. The findings reinforce a shift toward more adaptable, cosmetically acceptable topical therapies in dermatologic care.

Reference:

Gooderham MJ, Alonso-Llamazares J, Bagel J, et al. Roflumilast foam, 0.3%, for psoriasis of the scalp and body: the ARRECTOR phase 3 randomized clinical trial. JAMA Dermatol. 2025;161(7):698–706. doi:10.1001/jamadermatol.2025.1136