Ruxolitinib Consistent in Safety, Tolerability Over 52-Weeks in Children with Extensive Atopic Dermatitis

Treatment of children aged 2-11 years with extensive atopic dermatitis (AD) using ruxolitinib cream, 1.5% at a twice-per-day dosing regimen led to positive results, according to new late-breaking data presented at the Revolutionizing Atopic Dermatitis (RAD) 2024 Annual Meeting in Chicago.¹

These new 52-week results resulted from a maximum-use trial providing the first set of extended data following the initial 8-week ruxolitinib cream research conducted involving children with moderate to severe atopic dermatitis. These prior findings had highlighted the medication’s tolerability, safety, efficacy, and minimal systemic absorption.

Comprehensive data on safety, tolerability, systemic exposure, and both clinical and patient-reported outcomes are reported for the entire 52-week treatment period, assessing if the benefits and tolerability noted at Week 8 persist through the long-term safety period, concluding at Week 52.

Design and Findings

The investigators, led by Robert Bissonnette, MD, from Innovaderm Research, conducted their research as an open-label, single-arm Maximum-Use Trial (MUsT), assessing children in the age 2-11 bracket with 3 months minimum of eczema. The disease also had to have impacted at least 35% of these subjects’ body surface area (BSA).

In terms of other inclusion criteria, the participants also had to have applied ruxolitinib cream 1.5% on a twice-per-day regimen over 4 total weeks to baseline lesions, have an Investigator’s Global Assessment (IGA) score of 3 or greater, and have carried out as-needed application of the cream to any active lesions for a 4 more weeks. The subjects would then be allowed to join the as-needed long-term safety phase of the study occurring over 44 weeks.

A total of 29 children who also had moderate to severe disease were included over the 52 weeks, with 31% having reported treatment-emergent adverse events (AEs). A single participant was found by the team to have experienced 2 treatment-related reactions at the site of application (paresthesia and folliculitis), though Bissonnette et al. found no AEs had resulted in cessation of treatment or interruption and no serious events had suggested systemic Janus kinase (JAK) inhibition.

In the beginning 4-week, twice-daily continuous treatment period, the research team noted that the average (SD) amount of treatment applied was 8.5 (6.29) grams each day. The team noted that this led to a mean steady-state plasma concentration of 98.2 nM, which was far lower than the half-maximal concentration for JAK-mediated myelosuppression among patients in the adult range (281 nM).

They added that from the 8 to 52-week marks, over the course of the as-needed period, the average (SD) amount of cream applied had been shown to have diminished to 3.2 (2.79) grams each day. At the 4 and 52-week marks, it was shown that 53.8% of subjects received IGA–Treatment Success through an IGA score of 0/1 and a ≥2-grade improvement from baseline.

The investigators also found that the mean BSA impacted by eczema had lowered from 58.0% at the point of baseline to 11.4% at the 4-week mark. It further shrank to 2.2% by the 52-week mark.

The research team noted that the 52-week study period had also involved a recording of patient-reported outcomes such as Children's Dermatology Life Quality Index, Patient-Oriented Eczema Measure, and Infants' Dermatitis Quality of Life Index. Overall, consistent safety and tolerability had continued over the 52-week study in these children.

The team also acknowledged that the rapid clearance of subjects’ lesions that occurred with twice-per-day use over initial 4 weeks and had sustained with long-term use, indicated a manageable application burden as there had been small amounts of cream needed. These results add to the existing body of data surrounding ruxolitinib’s use for eczema.²

To learn more about this trial and other related topics, view the RAD 2024 conference coverage page.

References

1. ^{Bissonnette R, Lee M, Paller A, et al. Ruxolitinib cream 1.5% twice daily for the treatment of extensive atopic dermatitis in children aged 2–11 years: 52 week results from a maximum-use trial. Revolutionizing Atopic Dermatitis (RAD) 2024 Annual Meeting June 8 – 10, 2024. Chicago, IL.}
2. ^{Eichenfield, L.F., Simpson, E.L., Papp, K. et al. Efficacy, Safety, and Long-Term Disease Control of Ruxolitinib Cream Among Adolescents with Atopic Dermatitis: Pooled Results from Two Randomized Phase 3 Studies. Am J Clin Dermatol (2024). https://doi.org/10.1007/s40257-024-00855-2.}