Two phase III clinical trials demonstrated that once-daily roflumilast cream, 0.15%, may improve symptoms of atopic dermatitis within 4 weeks, according to a recent study.

In the Interventional Trial Evaluating Roflumilast Cream for the Treatment of Atopic Dermatitis 1 and 2 (INTEGUMENT-1 and INTEGUMENT-2) phase III randomized clinical trials, published in JAMA Dermatology, researchers evaluated the safety and efficacy of once-daily roflumilast cream, 0.15%, for treating mild to moderate atopic dermatitis (AD) in patients aged 6 years and older. A total of 1,337 participants from sites in the United States, Canada, and Poland were randomly assigned to receive either roflumilast cream or vehicle cream for 4 weeks. The primary endpoint was achieving Validated Investigator Global Assessment for AD (vIGA-AD) success at week 4, defined as “clear” or “almost clear” with a 2-grade improvement from baseline.

The investigators recruited 1,337 participants, with 654 enrolled in the INTEGUMENT-1 trial and 683 in the INTEGUMENT-2 trial. The average age of the participants was 27.7 years (standard deviation [SD] = 19.2), and 56.9% were female. On average, 13.6% of the body surface area was affected by AD, with an SD of 11.6% and a range from 3% to 88%.

For the primary endpoint of vIGA-AD success at week 4, in the INTEGUMENT-1 trial, 32.0% of the patients who received roflumilast achieved success compared with 15.2% among those who received vehicle, with a difference of 17.4% (P < .001). In the INTEGUMENT-2 trial, 28.9% of those treated with roflumilast met the endpoint vs 12.0% among those treated with vehicle, with a difference of 16.5% (P < .001).

In terms of achieving at least a 75% reduction in the Eczema Area and Severity Index (EASI-75), 43.2% of the participants in the roflumilast group in INTEGUMENT-1 reached this benchmark compared with 22.0% in the vehicle group (P < .001). In INTEGUMENT-2, 42.0% of the patients in the roflumilast group achieved EASI-75 vs 19.7% of those in the vehicle group (P < .001).

For itch reduction at week 4, patients who had a baseline Worst Itch Numeric Rating Scale (WI-NRS) score of 4 or higher experienced a decrease of at least 4 points on the scale, beginning as soon as 24 hours following treatment initiation. In INTEGUMENT-1, the nominal P-value was .004, and in INTEGUMENT-2, it was P < .001.

A greater proportion of patients treated with roflumilast achieved the primary endpoint compared with those receiving vehicle cream. Additionally, a higher percentage of roflumilast-treated patients achieved at least a 75% reduction in EASI-75 scores, and more patients reported a reduction in itch on the WI-NRS, with differences apparent as early as 24 hours after initial application.

Roflumilast was well tolerated across both trials, with low rates of treatment-emergent adverse events. Over 95% of the participants had no signs of irritation at the application site as assessed by investigators, and over 90% reported no or mild sensations at the application site. 

Full disclosures can be found in the published study.