INTEGUMENT-OLE: Roflumilast Cream Maintains Long-Term Disease Control in Pediatric and Adolescent Atopic Dermatitis

Long-term results from the INTEGUMENT-OLE study demonstrate sustained improvements in signs, symptoms, and quality of life in patients aged ≥2 years with atopic dermatitis (AD) treated with once-daily or twice-weekly roflumilast (Zoryve) cream, according to data presented at the 2025 Revolutionizing Atopic Dermatitis (RAD) Conference in Nashville.

The phase 3, multicenter, open-label extension (OLE) enrolled 1220 patients from prior pivotal INTEGUMENT trials: INTEGUMENT-1/2 (patients aged ≥6 years; n = 658) and INTEGUMENT-PED (patients aged 2–5 years; n = 562). Patients who completed the 4-week parent trials without safety concerns received roflumilast cream 0.15% (≥6 years) or 0.05% (2–5 years) for up to 52 weeks.

At week 56, Investigator Global Assessment for AD (vIGA-AD) scores of 0/1 (clear or almost clear) were achieved by 55.7% of patients aged ≥6 years and 63.1% of patients aged 2–5 years. A more than 2-point vIGA-AD improvement from baseline (vIGA-AD success) was achieved in 49.0% and 54.2% of the older and younger groups, respectively.

Improvements in itch, assessed by the Worst Itch Numeric Rating Scale (WI-NRS), were also maintained. Among patients aged ≥6 years with baseline WI-NRS ≥4, 60.7% achieved a ≥4-point improvement by week 56; in those aged 2–5 years, the response rate was 55.3%.

Body surface area (BSA) involvement decreased from baseline in both cohorts. In patients aged ≥6 years, the mean BSA improved from 14.8% at parent study baseline to 3.7% at week 56. In children aged 2–5 years, BSA improved from 22.3% to 4.9% over the same period.

Patients achieving vIGA-AD 0 could transition from once-daily to proactive twice-weekly (BIW) application. Disease control, defined as the duration of vIGA-AD 0/1 with adequate symptom management, was sustained with a median Kaplan-Meier estimated duration of 281 days (95% CI, 147–not estimable) in patients aged ≥6 years and 238 days (95% CI, 146–331) in those aged 2–5 years.

Researchers also reported that roflumilast cream was well tolerated across age groups. Treatment-related adverse events occurred in 4.7% of patients from INTEGUMENT-1/2 and 2.5% of those from INTEGUMENT-PED. Application-site pain was infrequent, reported in only 0.5% and 0.7% of patients, respectively. No new safety signals emerged during the long-term treatment period.

“These data support the long-term use of roflumilast cream as a safe and effective steroid-sparing topical for managing pediatric and adolescent AD,” the authors concluded. Notably, proactive BIW application was effective in maintaining remission following disease clearance.

Roflumilast cream 0.15% is currently approved in the US for the treatment of mild-to-moderate AD in people aged ≥6 years. The INTEGUMENT-OLE study further supports its potential as a long-term maintenance therapy in younger populations.