For pediatric and adult patients with mild-to-moderate AD, roflumilast cream demonstrated a significant benefit over placebo. In addition, the drug provided an encouraging safety profile. Around 30% of patients reached a validated Investigator’s Global Assessment for AD (vIGA) of 0/1. Itch reduction after the first day of treatment was also significant.
Two phase 3 studies on topical treatment of AD, INTEGUMENT-I and INTEGUMENT-II, explored this possible new indication for the phosphodiesterase 4 inhibitor approved in 2022 by the FDA for psoriasis. Lawrence Eichenfield, MD, presented these finding at the 2023 American Academy of Dermatology annual meeting.1
A total of 1,337 patients were randomized to a vehicle or once-daily roflumilast 0.15% cream use over 4 weeks. Participants had to be at least age 6 with mild/moderate AD. Researchers stressed that almost 50% of the participants were pediatric patients aged 5‒17. Around one-third of participants in both trials presented a vIGA of 3 at baseline, mean Eczema Area and Severity Index (EASI) scores ranged from 9.8-10.3, and mean Worst Itch Numeric Rating Scale (WI-NRS) values from 5.9-6.2.
The proportions of participants achieving the primary endpoint of vIGA of clear or almost clear skin plus a two-grade improvements at week 4 of INTEGUMENT-1 and -2 were significantly higher in the roflumilast arms than in the vehicle groups: 32.0% versus 15.5% (P<0.0001) and 28.9% versus 12.0% (P<0.0001). Also, the EASI75 results were in favor of roflumilast cream at 43.2% versus 22.0% and 42.0% versus 19.7%, with a significance level of P<0.0001 for both INTEGUMENT trials. Notably, a considerable advantage of roflumilast in INTEGUMENT-1 started as early as 1 week after the beginning of therapy.
Since itch is a key symptom of AD, reaching a ≥ 4-point or more reduction was also evaluated as secondary endpoint: in study 1, the ratios were 33.6% versus 20.7% at week 4 (P=0.0089) and the respective results in trial 2 were 30.2% versus 12.4% (P=0.0014). Dr. Eichenfield pointed out that an itch improvement was observed at 24 hours after the first application of roflumilast.
Headache, nausea, application site pain, and nasopharyngitis were most common treatment-emergent adverse effects but none occurred at a rate above 3.5% in the roflumilast groups. Thus, the investigators assigned an overall favorable safety and tolerability profile to the active treatment.
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