Once-Daily Roflumilast Cream Shows Promising for Atopic Dermatitis: JAMA

To address this, two phase 3 clinical trials, INTEGUMENT-1 and INTEGUMENT-2, were conducted to evaluate the efficacy and safety of roflumilast cream in children and adults with mild to moderate AD. The participants were aged 6 years and older with mild to moderate AD, as assessed on a scale of 0 (clear) to 4 for the Validated Investigator Global Assessment for Atopic Dermatitis (VIGA-AD). Participants were randomly assigned in a 2:1 ratio to either receive roflumilast cream, 0.15%, or vehicle cream once daily for four weeks.

The primary efficacy outcomes were VIGA-AD success at week 4, which was a score of 0 or 1 with at least a 2-grade improvement from baseline. Secondary outcomes were at least a 75% reduction in the Eczema Area and Severity Index (EASI-75) and improvements in the Worst Itch Numeric Rating Scale. Safety, local tolerability, and treatment-emergent adverse events (TEAEs) were also measured.

Key Findings

There were 1,337 patients who enrolled in total: 654 in INTEGUMENT-1 and 683 in INTEGUMENT-2. The age was a mean of 27.7 years (SD, 19.2); 56.9% were female. The BSA affected was a mean of 13.6% (SD, 11.6%; 3.0%-88.0%).

• INTEGUMENT-1 RoJamie was significantly better than vehicle regarding the proportion of patients achieving VIGA-AD success by determining 32.0% with roflumilast vs. 15.2% with vehicle (p<0 .001).

• INTEGUMENT-2 was 28.9% vs. 12.0% with vehicle (p<0.001).

EASI-75 Response at Week 4:

• INTEGUMENT-1: 43.2% of roflumilast-treated patients reached EASI-75 compared to 22.0% of vehicle-treated patients (p<0.001).

• INTEGUMENT-2: 42.0% vs. 19.7%, respectively (p<0.001).

Safety and Tolerability:

• Roflumilast was generally well tolerated with low rates of TEAEs.

• At all time points, ≥95% of patients receiving roflumilast were free of signs of irritation at the application site.

• 90% of roflumilast-treated patients were free of or had mild sensation at the application site.

The phase 3 trials showed that once-daily roflumilast cream, 0.15%, is effective for improving AD symptoms with a good safety profile. These results open the possibility for using this cream as an effective topical treatment option for mild to moderate AD in pediatric and adult patients.

Reference:

Simpson EL, Eichenfield LF, Alonso-Llamazares J, Draelos ZD, Ferris LK, Forman SB, Gooderham M, Gonzalez ME, Hebert AA, Kircik LH, Lomaga M, Moore A, Papp KA, Prajapati VH, Hanna D, Snyder S, Krupa D, Burnett P, Almaraz E, Higham RC, Chu DH, Berk DR. Roflumilast Cream, 0.15%, for Atopic Dermatitis in Adults and Children: INTEGUMENT-1 and INTEGUMENT-2 Randomized Clinical Trials. JAMA Dermatol. 2024 Nov 1;160(11):1161-1170. doi: 10.1001/jamadermatol.2024.3121. PMID: 39292443; PMCID: PMC11411450.