(101) Improvement in atopic dermatitis signs and symptoms with once-daily and proactive twice-weekly roflumilast cream 0.15% or 0.05%: results from the 52-week phase 3 INTEGUMENT-OLE trial in patients aged ≥2 years

Background: : Efficacy and safety of roflumilast cream 0.15%/0.05% once daily (QD) for mild-to-moderate atopic dermatitis (AD) in patients aged ≥6 years (y) and 2–5 y were demonstrated in pivotal 4-week (wk) randomized, vehicle-controlled, phase 3 trials (INTEGUMENT [INT] -1/2 and INT-PED, respectively).

Objective: : Evaluate safety, sign/symptom improvements, and duration of disease control following AD clearance during long-term treatment with roflumilast cream 0.15%/0.05%.

Methods: : Eligible patients who completed INT-1/2 or INT-PED could enroll in the open-label extension (INT-OLE/NCT04804605). Roflumilast cream 0.15% (≥6 y) or 0.05% (2–‍5 y) was applied QD for up to 52 wks. Patients who achieved Validated Investigator Global Assessment for AD (vIGA-AD) of clear (0) at/after OLE wk 4 switched to twice-weekly (BIW) application, which was continued as long as adequate ‘disease control’ (ie, vIGA-AD clear/almost clear [0/1] and AD sign/symptom control) was maintained. Efficacy endpoints, assessed from parent study baseline, included vIGA-AD 0/1, Worst Itch-Numeric Rating Scale (WI-NRS) of no/minimal itch (0/1), and mean body surface area affected (BSA) over time. Safety and application-site tolerability were assessed.

Results: : At OLE wk 52, vIGA-AD 0/1 rates were 55.7% (117/210) in the INT-1/2 population and 63.1% (234/371) in the INT-PED population; WI-NRS 0/1 rates were 47.1% (49/104) and 40.7% (116/285), respectively. Mean BSA decreased from parent-study baseline to OLE wk 52 for patients from INT-1/2 (14.8% to 3.7%) and INT-PED (22.3% to 4.9%). Among patients who switched to BIW application after AD clearance (INT-1/2: 19.8% [130/658]; INT-PED: 30.2% [170/562]), median durations of disease control (Kaplan–Meier estimates) were 281 days and 238 days, respectively. In the OLE, rates of treatment-related AEs were 4.7% (31/657) for INT-1/2 and 2.5% (14/562) for INT-PED. Application-site pain was reported for 0.5% and 0.7% of patients from INT-1/2 and INT-PED, respectively. During any OLE visit, 0.4%–2.1% of patients self-reported stinging and/or burning that caused definite discomfort.

Conclusions: : In patients aged ≥2 y with AD, roflumilast cream 0.15%/0.05% decreased AD signs/symptoms, including BSA, and maintained improvements with long-term treatment. Patients who switched to BIW application maintained vIGA-AD 0/1 and adequate sign/symptom control for >200 days. Roflumilast cream was well tolerated, making it is an appropriate alternative to topical corticosteroids and calcineurin inhibitors for AD.

Sponsorship:: Arcutis Biotherapeutics, Inc.