INTEGUMENT: Quality of Life with Roflumilast Cream (Zoryve) in Atopic Dermatitis

New data have shown that roflumilast cream (Zoryve) 0.15% and 0.05% improved quality of life in patients aged 2 years and older with atopic dermatitis significantly, with particular improvements in sleep and long-term disease control.1

Arcutis Biotherapeutics, Inc., announced these recent data on roflumilast cream, presenting them at the 2025 Fall Clinical Dermatology conference in Las Vegas. Roflumilast cream is a topical formulation of a highly selective phosphodiesterase type 4 (PDE4) inhibitor, an established target in dermatology designed to regulate inflammatory signaling.

“Sleep disruption is a persistent and often overlooked but very real daily burden for those impacted by atopic dermatitis, including young children and their families,” Mercedes E. Gonzalez, MD, INTEGUMENT-PED clinical trial investigator and lead author of the poster, said in a statement.1

By inhibiting PDE4, roflumilast can help to decrease the production of pro-inflammatory mediators, thereby diminishing skin inflammation and restoring immune balance. These recent findings on this topical agent resulted from three phase 3 randomized, controlled trials: INTEGUMENT-1, INTEGUMENT-2, and INTEGUMENT-PED.

These studies collectively demonstrated that once-daily roflumilast cream led to substantial reductions in pruritus and improved sleep quality compared with vehicle. During the INTEGUMENT-1 and INTEGUMENT-2 studies, which involved subjects aged 6 years and older, 884 such patients were treated with roflumilast cream 0.15% and 453 were in the vehicle arm.

During the INTEGUMENT-PED analysis, involving patients aged 2 - 5 years with caregiver-applied treatment, 436 received the topical cream (roflumilast 0.05%) and 215 received vehicle. Across all of these studies, the topical cream was shown by Gonzalez et al to have reduced the impact of atopic dermatitis on sleep among patients and their families compared with the vehicle.

Findings were also consistent across both age cohorts. Roflumilast cream also significantly improved itch, as determined by the patients’ daily Worst Itch Numeric Rating Scale (WI-NRS) scores. From the point of baseline, improvements at the 4-week mark were noted as greater with the topical cream than with vehicle in both INTEGUMENT-1/2 (2.6 versus 1.6; P < .001) and INTEGUMENT-PED (2.6 versus 1.6; P < .01).

Additionally, Gonzalez and colleagues found greater reductions in mean WI-NRS scores took place within 24 hours of the first application in roflumilast cream-treated subjects compared with those in the vehicle arm (P < .005) in both study sets. The cream was aslo found by the investigators to be well-tolerated across analyses, with treatment-related adverse events (AEs) and serious AEs being observed in ≤6% and <1% of patients, respectively. Application-site pain was reported in 1.5% of those included in INTEGUMENT-1/2 and 1.6% of those in INTEGUMENT-PED.

Long-term results were also highlighted from the phase 3 INTEGUMENT-OLE study, designed as a multicenter, open-label extension analysis of roflumilast cream in individuals aged 2 years and older with mild-to-moderate atopic dermatitis. These data also supported the drug’s efficacy and safety, with sustained or improved clinical responses being observed among participants who had completed 1 of the pivotal phase 3 trials (INTEGUMENT-1 or INTEGUMENT-2 or INTEGUMENT-PED).

In children aged 2 to 5 years, who are known to typically present with higher body surface area (BSA) involvement, mean BSA affected was shown by the investigative team to have dipped from 22.3% to 4.9% in INTEGUMENT-PED, while in the INTEGUMENT-1/2 population, mean BSA dipped from 14.8% to 3.7% over an additional 52 weeks of therapy. Beginning at the 4-week mark, those attaining a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD3) score of “Clear” (0) transitioned to proactive 2 times-weekly maintenance dosing (roflumilast cream 0.05%, n=170 [30.2% of subjects aged 2–5 years]; roflumilast cream 0.15%, n=130 [19.8% of subjects aged ≥6 years]).

Investigators noted median duration of disease control, defined as maintaining vIGA-AD “Clear” or “Almost Clear” with adequate management of symptoms, had been 238 days in children aged 2 - 5 years and 281 days in those aged 6 years and older. By the 56-week mark, the percentage of individuals attaining vIGA-AD “Clear” or “Almost Clear” (0/1) rose to 55.7% in the INTEGUMENT-1/2 population and 63.1% in the INTEGUMENT-PED population, versus 41.3% and 40.3%, respectively, at Week 4.

In a similar finding, the investigative team highlighted the proportion of individuals reporting WI-NRS scores of no or minimal itch (0/1) increased from 25.5% at the 4-week mark to 41.4% in INTEGUMENT-1/2 and 40.7% in INTEGUMENT-PED at the 56-week mark. During the OLE phase, the team found treatment-related AEs were infrequent.

“[Roflumilast cream] offers a safe, nonsteroidal, and targeted treatment option,” Gonzalez said in her statement.1 “In addition, these results highlight the clinically meaningful benefit of [roflumilast] cream on reducing itch and improving sleep in young children with atopic dermatitis.”

References

1. Arcutis to Present New Quality of Life and Long-Term Data with ZORYVE® (roflumilast) Cream 0.15% and 0.05% for the Treatment of Atopic Dermatitis at the Fall Clinical Dermatology Conference. Arcutis Biotherapeutics, Inc. October 24, 2025. https://investors.arcutis.com/news-releases/news-release-details/arcutis-present-new-quality-life-and-long-term-data-zoryver/.

2. Smith T. Roflumilast Cream 0.05% Effective for Atopic Dermatitis in Patients Aged 2-5 Years. HCPLive. February 22, 2025. Accessed October 24, 2025. https://www.hcplive.com/view/roflumilast-cream-0-05-effective-atopic-dermatitis-patients-aged-2-5-years.