AAD Pediatric AD Guidelines Back Roflumilast, Ruxolitinib, Tapinarof

Dermatology Times recently covered the American Academy of Dermatology's (AAD) first updated pediatric atopic dermatitis (AD) guideline in more than a decade, highlighting its recommendations for earlier use of biologics and oral Janus kinase (JAK) inhibitors for moderate to severe disease.¹ The newly published guideline also provides detailed evidence supporting strong recommendations for 3 newer nonsteroidal topical therapies—roflumilast cream, ruxolitinib cream, and tapinarof cream—expanding the steroid-sparing treatment options available for children.

Guideline Strengthens Topical Treatment Recommendations

The updated guideline, published in the Journal of the American Academy of Dermatology, includes 27 evidence-based recommendations developed through a systematic review using the GRADE framework.¹ Among them are strong, high-certainty endorsements for roflumilast, ruxolitinib, and tapinarof for children as young as 2 years old, significantly expanding the steroid-sparing topical armamentarium.

Topical corticosteroids and calcineurin inhibitors have long served as the foundation of pediatric AD treatment, but concerns regarding skin atrophy, application-site burning, and boxed-warning language have prompted interest in effective nonsteroidal alternatives. Crisaborole, approved for patients aged 3 months and older, was the first widely adopted option in this class. The updated guideline now extends strong recommendations to 3 additional therapies, providing clinicians with more choices across the pediatric age spectrum.

Roflumilast Shows Strong Once-Daily Efficacy

The workgroup based its recommendation for roflumilast cream on 4 randomized controlled trials, including the phase 3 INTEGUMENT-PED study in children aged 2 to 5 years with mild-to-moderate AD.² Once-daily roflumilast cream (0.05% for children aged 2-5 years and 0.15% for patients aged 6 years and older) significantly increased Eczema Area and Severity Index (EASI) 75 response compared with vehicle after 28 days (relative risk [RR], 2.02; 95% CI, 1.72-2.37).

Ruxolitinib Demonstrates Potent Disease Control

For ruxolitinib cream, a topical JAK inhibitor approved for patients aged 2 years and older whose disease is inadequately controlled with other topical therapies, the guideline cites 3 randomized clinical trials, including the pediatric-specific TRuE-AD3 study in children aged 2 to 11 years.³ Across studies, ruxolitinib significantly reduced EASI scores and increased Investigator Global Assessment (IGA) 0/1 responses compared with vehicle. A network meta-analysis included in the guideline also found efficacy comparable with potent topical corticosteroids, including betamethasone valerate 0.1%.

Tapinarof Produced the Largest Efficacy Estimates

Among the 3 agents, tapinarof cream demonstrated the largest efficacy estimates in the pivotal phase 3 ADORING trials, in which more than 80% of participants were children.⁴ Tapinarof significantly improved EASI 75 response (RR, 2.60; 95% CI, 2.06-3.29), meaningful itch response (RR, 1.77; 95% CI, 1.43-2.19), and validated Investigator Global Assessment for AD (vIGA-AD) success (RR, 2.89; 95% CI, 2.16-3.86) compared with vehicle.

Although all 3 therapies received strong recommendations, the guideline notes important differences among them. Roflumilast offers once-daily phosphodiesterase-4 inhibition with minimal application-site reactions, ruxolitinib provides potent anti-inflammatory activity with efficacy comparable to high-potency topical corticosteroids, and tapinarof demonstrated the greatest overall efficacy estimates while carrying unique safety considerations.

Safety Profiles Influence Treatment Selection

Safety profiles were generally favorable across all 3 agents, although each carries distinct considerations that may influence treatment selection. Application-site pain and stinging were the most common adverse events with crisaborole and, to a lesser extent, roflumilast; treatment-emergent adverse events with roflumilast were not meaningfully higher than vehicle across clinical trials. Tapinarof was associated with a modest increase in treatment-related adverse events, primarily folliculitis and acneiform eruptions, which the guideline recommends discussing with families before treatment initiation.

Boxed Warning Shapes Ruxolitinib Use

Ruxolitinib carries a boxed warning extrapolated from safety findings with oral tofacitinib, including risks of serious infection, malignancy, major adverse cardiovascular events, and thrombosis, despite these signals not being observed in topical ruxolitinib trials. Accordingly, the guideline recommends limiting application to no more than 20% body surface area because of systemic absorption considerations and suggests reserving the therapy for patients without risk factors related to the boxed-warning conditions.

Treatment Algorithm Places New Topicals Alongside Steroids

The guideline's treatment algorithm positions roflumilast, ruxolitinib, and tapinarof alongside topical corticosteroids and calcineurin inhibitors as first-line options for inflamed skin, while reserving phototherapy and systemic therapies for patients whose disease remains uncontrolled despite optimized topical treatment.

Together, the recommendations signal a broader shift toward individualized topical management in pediatric AD. Rather than relying primarily on topical corticosteroids, clinicians now have 4 strongly recommended steroid-sparing therapies—including crisaborole—with distinct mechanisms of action, dosing schedules, and safety profiles that can be tailored to patient age, disease distribution, and treatment goals. The workgroup also emphasized the need for future head-to-head studies comparing these newer agents with generic topical corticosteroids in terms of efficacy, safety, and cost-effectiveness.

REFERENCES:

1. Davis DMR, Alikhan A, Bercovitch L, et al. Guidelines of care for the management of atopic dermatitis in pediatric patients. J Am Acad Dermatol. 2026;95(1):121.e1-121.e26. doi:10.1016/j.jaad.2026.02.113 https://www.jaad.org/article/S0190-9622(26)00343-9/fulltext
2. Eichenfield LF, Serrao R, Prajapati VH, et al. Efficacy and safety of once-daily roflumilast cream 0.05% in pediatric patients aged 2-5 years with mild-to-moderate atopic dermatitis (INTEGUMENT-PED): a phase 3 randomized controlled trial. Pediatr Dermatol. 2025;42(2):296-304. 10.1111/pde.15840
3. Eichenfield LF, Stein Gold LF, Simpson EL, et al. Efficacy and safety of ruxolitinib cream in children aged 2 to 11 years with atopic dermatitis: results from TRuE-AD3, a phase 3, randomized double-blind study. J Am Acad Dermatol. 2025;93(3):689-698. 10.1016/j.jaad.2025.05.1385
4. Silverberg JI, Eichenfield LF, Hebert AA, et al. Tapinarof cream 1% once daily: significant efficacy in the treatment of moderate to severe atopic dermatitis in adults and children down to 2 years of age in the pivotal phase 3 ADORING trials. J Am Acad Dermatol. 2024;91:457-465. 10.1016/j.jaad.2024.05.023