Early Trial Finds Ruxolitinib Cream Safe, Effective Among Children With AD

Ruxolitinib cream was well-tolerated in pediatric patients with atopic dermatitis (AD), according to recent study results. The treatment had no effect on blood counts or bone biomarkers, suggesting it had no impact on bone formation or bone metabolism in these young patients.

Findings were published in the journal Annals of Allergy, Asthma, and Immunology and also showed mean plasma concentration was low among patients receiving the treatment. Efficacy was similar to data reported in previous studies carried out among adolescents and adults, authors noted.

More than 20% of children around the world are affected by AD, and around one-third of these patients have moderate to severe forms of the chronic, inflammatory skin condition.

“Children with AD experience chronic and relapsing episodes of intense itching, sleep disturbances, and mental health comorbidities, affecting the quality of life of the patients and their caregivers,” researchers wrote. In addition, current therapies for children with AD have safety and tolerability concerns that could limit long-term use.

Ruxolitinib cream, which is a topical formulation of the Janus kinase inhibitor (JAK)1/JAK2 inhibitor ruxolitinib, has been approved by the FDA for treatment of mild to moderate AD in children aged 12 or older.

In the current phase 1 study, investigators sought to evaluate safety and tolerability of the treatment in children aged 2 to 17 who were diagnosed with AD. Patients were enrolled in the study between September 2017 and October 2020.

“As part of the safety assessment, select bone biomarkers in serum were investigated in children younger than 12 years to evaluate any possible impact of ruxolitinib on bone growth,” they explained.

The open-label, increasing-strength study included 71 patients from 17 study sites across the country. All participants had involvement of 8% to 20% body surface area (BSA) (excluding scalp), and had an Investigator’s Global Assessment (IGA) score of 2 or higher (mild to severe).

The children were divided into 6 cohorts to apply 0.5%, 0.75%, or 1.5% ruxolitinib cream twice daily for 28 days. Researchers analyzed efficacy, safety, and pharmacokinetics, at baseline, day 10 and day 29.

At baseline, 44 patients had an IGA score of 3, while median BSA affected was 12.2% (range 1.7%-20.4%). The majority of patients were female and white. Average treatment adherence rates were 98.7% to 100% across all 6 cohorts.

Data showed:

• Ruxolitinib cream was well tolerated, with 4 patients (5.6%) experiencing treatment-related adverse events (all grades 1/2)
• No clinically meaningful changes in mean chemistry or hematology values were observed, and no consistent pattern of change in bone biomarkers was detected
• Mean plasma ruxolitinib levels within each cohort (range, 23.1-97.9 nM) were well below the half-maximal inhibitory concentration for thrombopoietin phosphorylation of STAT3 (281 nM)
• All cohorts experienced improvements in exploratory efficacy end points

Treatment-emergent adverse events included headache, AD worsening, neutropenia, and upper respiratory tract infection. Application site reactions were also infrequent, authors added.

“In this study, ruxolitinib cream was well tolerated at different strengths in children and adolescents aged 2 to 17 years with AD,” they said.

“Although this was an open-label study without a placebo control, the [treatment-emergent adverse events] observed were consistent with those observed in phase 3 studies of ruxolitinib cream in adolescents (12-17 years) and adults with AD.”

Small cohort sizes marked a limitation, particularly for measurements of drug accumulation among younger cohorts, researchers noted. Treatment duration was also limited to just four weeks, and patients with more extensive AD were not included in the trial.

Overall, the treatment “may offer benefit in patients who do not respond to topical steroids, on the basis of the difference in mechanisms of action between the 2 treatments,” authors concluded.

However, they note “further studies to evaluate the use of ruxolitinib cream in children are warranted.”

Reference

Leung DYM, Paller AS, Zaenglein AL, et al. Safety, pharmacokinetics, and efficacy of ruxolitinib cream in children and adolescents with atopic dermatitis. Ann Allergy Asthma Immunol. Published online December 27, 2022. doi:10.1016/j.anai.2022.12.033