Ruxolitinib Cream Shows Lasting Results in Pediatric Max-Use Trial

Results of a recently published maximum-use study underscore the safety and efficacy of 1.5% ruxolitinib cream in children aged 2 to 11 years with extensive, moderate to severe atopic dermatitis (AD).¹ “We welcome the availability of topical nonsteroidal to expand our armamentarium of safe treatments for children with atopic dermatitis, especially in sensitive areas,” said Amy Paller, MD, chair of the Department of Dermatology at Northwestern University’s Feinberg School of Medicine in Chicago, Illinois, and one of the study’s authors.

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AD affects over 10% of children worldwide, yet conventional topical treatments, including corticosteroids and calcineurin inhibitors, can cause skin thinning and potential systemic adverse events.^2,3 Ruxolitinib cream (Opzelura; Incyte), a selective JAK1/JAK2 inhibitor, has shown efficacy and safety in adult and adolescent populations with mild to moderate AD.⁴ Paller said the phase 1 trial (NCT05034822) found that “the efficacy and safety of use of this cream for AD in children is sustained during a full year of treatment.”

Background

The study results emphasized AD’s chronic nature, and the limitations of existing treatments underscore the need for novel therapies. JAK signaling pathways are pivotal in mediating inflammation, itch, and skin barrier dysfunction, making them a viable therapeutic target.⁵ Ruxolitinib cream has demonstrated favorable outcomes in earlier studies, providing rapid symptom relief and maintaining disease control with long-term use.¹

Study Design and Methods

The open-label study enrolled children aged 2 to 11 years with moderate to severe AD (≥ 35% body surface area [BSA] affected). Patients underwent a 4-week maximum-use period with continuous twice-daily application of 1.5% ruxolitinib cream, followed by a 4-week treatment-extension phase for active lesions only. Those achieving a 20% or lower BSA involvement at week 8 entered a long-term safety (LTS) phase with as-needed application through week 52. Assessments included safety (primary end point), pharmacokinetics, efficacy, and quality-of-life (QOL) measures.

Results

Twenty-nine patients participated, with a median age of 5 years. Mean baseline BSA involvement was 58%, with 82.8% of patients having prior topical treatment experience. The investigators stated that most (96.6%) completed the 4-week maximum-use period, and 63.6% completed the LTS phase.

The ruxolitinib cream was well tolerated, with treatment-emergent adverse events (TEAEs) reported in 31% of patients, none of which were serious or led to treatment discontinuation. The most common TEAEs were upper respiratory infections, gastrointestinal symptoms, and application site reactions. Notably, the investigators stated no adverse events of special interest related to systemic JAK inhibition were observed.

According to the study results, plasma concentrations of ruxolitinib during the maximum-use period were below the threshold for JAK-mediated myelosuppression, even in patients with high BSA involvement (> 50%). Mean daily cream usage decreased substantially during the LTS phase, correlating with reduced lesion burden.

The investigators reported significant reductions in affected BSA, with mean involvement decreasing from 58% at baseline to 2.2% by week 52. Rapid improvements in Investigator’s Global Assessment and Eczema Area and Severity Index (EASI) scores were achieved, with 84% of patients attaining EASI-75 at week 8. Itch relief, as measured by the numerical rating scale, was reported to be rapid and sustained, with a median time to significant improvement of 4 days. The investigators noted that QOL measures, including sleep, depressive symptoms, and family impact, showed substantial improvement from baseline and were sustained throughout the study.

Furthermore, Paller said that the majority of feedback from patients and caregivers has been positive. “People like applying something that is not greasy, and effectiveness has been good. Importantly, there has not been burning or stinging with the product,” she said. “I will note that it is a twice-daily application per label, so this presents a bit more of a burden than a once-daily product, but as with other twice-daily products, it presents the opportunity for reducing to daily use as maintenance, although testing for this option has not been performed.”

Conclusion

The investigators found that ruxolitinib cream demonstrated consistent safety and efficacy in pediatric patients with extensive AD. The trial’s novel design, including long-term safety evaluation, supports ruxolitinib cream’s use as an effective nonsteroidal option for this challenging population. Minimal systemic absorption and the absence of significant safety signals enhance its appeal for broader application. “These data provide more evidence of safety. The on-label limit for use in AD is 20% body surface area, which provides even more assurance of not having systemic absorption,” Paller said. The investigators suggested that future studies with larger cohorts may further validate these findings and explore extended indications.

References

1. Stein Gold L, Bissonnette R, Forman S, et al. A maximum-use trial of ruxolitinib cream in children aged 2-11 years with moderate to severe atopic dermatitis. Am J Clin Dermatol. Published online January 6, 2025. doi:10.1007/s40257-024-00909-5
2. Langan SM, Irvine AD, Weidinger S. Atopic dermatitis. Lancet. 2020;396(10247):345-360. doi:10.1016/S0140-6736(20)31286-1
3. Wollenberg A, Barbarot S, Bieber T, et al. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II. J Eur Acad Dermatol Venereol. 2018;32(6):850-878. doi:10.1111/jdv.14888
4. Papp K, Szepietowski JC, Kircik L, et al. Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: Results from 2 phase 3, randomized, double-blind studies. J Am Acad Dermatol. 2021;85(4):863-872. doi:10.1016/j.jaad.2021.04.085
5. Huang IH, Chung WH, Wu PC, Chen CB. JAK-STAT signaling pathway in the pathogenesis of atopic dermatitis: an updated review. Front Immunol. 2022;13:1068260. doi:10.3389/fimmu.2022.1068260