Discussing New Findings on Ruxolitinib for Children with Eczema, with Linda Stein Gold, MD

No clinically meaningful changes were observed in hematologic parameters seen following 8 weeks of twice-per-day treatment with 1.5% ruxolitinib cream among children in the age range of 2-11 years with mild-to-moderate atopic dermatitis (AD), according to new research.

These new phase 3 findings on ruxolitinib resulted from the TRuE-AD3 study, and the findings suggest that the cream’s use among children with atopic dermatitis, or eczema, may lead to limited plasma concentrations of ruxolitinib. The drug’s use also suggests no hematologic laboratory shifts which would be indicative of systemic JAK-inhibition.

The TRuE-AD3 study was a randomized, double-blind, vehicle-controlled phase 3 trial. The HCPLive editorial team discussed these new data with Linda Stein Gold, MD, a trial investigator, vice president of the American Academy of Dermatology, and the head of the Henry Ford Health System division of dermatology.

HCPLive: Could you explain the mechanism by which ruxolitinib cream limits plasma concentrations and avoids systemic JAK inhibition?

Stein Gold: Ruxolitinib cream is designed to treat the skin directly with minimal systemic absorption. It was created with a purposeful molecular design for properties of molecular weight, polarity, lipophilicity, and number of aromatic rings to maximize concentrations in dermis/epidermis. Ruxolitinib cream allows for adequate solubility to achieve high enough concentrations to drive the first order diffusion across the keratinized stratum corneum.

It also allows for adequate permeability to rapidly establish a dynamic equilibrium. The hydrophilic-lipophilic balance allows the drug to partition out of the hydrophobic epidermis and into the hydrophilic dermis. It has a high clearance and short intrinsic half-life to enable quick elimination of any fraction of the dose that reaches systemic circulation.

HCPLive: Can you highlight the major findings of TRuE-AD3? What is the significance of the hematologic laboratory safety results?

Stein Gold: The goal of this study was to determine if hematologic changes are observed with ruxolitinib cream in children aged 2-11 with mild to moderate AD. There were no clinically meaningful changes in hematologic parameters with 8 weeks of twice daily ruxolitinib cream (0.75% or 1.5%).

Patients treated between 3-20 % body surface area. Mean plasma concentrations of ruxolitinib cream remained below a threshold associated with bone marrow myelosuppression with both strengths of ruxolitinib cream across age subgroups.

HCPLive: What are the implications of no clinically meaningful changes in hematologic parameters observed with the 8-week treatment in children?

Stein Gold: I feel more confident in the safety of ruxolitinib cream in patients age 2-11.

HCPLive: How do these findings compare to other topical treatments for atopic dermatitis in terms of safety and efficacy?

Stein Gold: I have confidence in the safety and efficacy of currently available topical medications for atopic dermatitis. Ruxolitinib cream provides increased efficacy, good safety and tolerability.

HCPLive: What are the next steps in the research and development of ruxolitinib cream for pediatric patients with atopic dermatitis?

Stein Gold: I am hopeful that we will see trials in even younger patients, age 3 months and older.

HCPLive: How might these findings impact the long-term management of atopic dermatitis in children, particularly those with mild to moderate forms of the disease?

Stein Gold: We have a long-term (52 weeks) tolerability, safety, systemic exposure, disease control, and impact on PROs of 1.5% ruxolitinib cream in children age 2-11 with extensive moderate to severe AD in a maximum use trial with body surface area >35%.

This trial found that 4 weeks of continuous-use twice daily led to rapid lesion clearance, which was maintained with as-needed use through Week 52. I find it reassuring to see the good safety and efficacy profile long term use in moderate to severe patients.

The quotes contained in this Q&A summary were edited for the purposes of clarity.