Hematologic Safety of Ruxolitinib Cream in Children with Atopic Dermatitis

New findings from the TRuE-AD3 phase 3 study (NCT04921969) highlight the hematologic laboratory safety results of twice-daily application of 1.5% ruxolitinib cream (Opzelura; Incyte) in children aged 2-11 years with mild to moderate atopic dermatitis (AD). Conducted with rigorous attention to detail, this study brings forth promising results indicating no clinically meaningful changes in hematologic parameters after 8 weeks of treatment. These outcomes suggest that the application of ruxolitinib cream in children with AD results in limited plasma concentrations of ruxolitinib and no hematologic laboratory changes indicative of systemic JAK inhibition.

Linda Stein Gold, MD

In a recent interview with Dermatology Times, Linda Stein Gold, MD, director of clinical research and division head of dermatology at Henry Ford Health System in Detroit, Michigan, elaborated on the study design, methodology, and the significance of the findings.

Study Design and Methodology

When asked about the study design and methodology, Stein Gold explained, “Hematologic laboratory assessments were collected at baseline, week 2, and week 8, and plasma concentrations of ruxolitinib cream were evaluated at either week 2 or 4 and at week 8. Baseline mean hemoglobin, platelet, and neutrophil counts were similar across treatment groups. No clinically meaningful changes from baseline in hemoglobin, platelet, and neutrophil counts were observed with either strength of ruxolitinib cream over 8 weeks.”

Robustness of Hematologic Safety Measures

Addressing the robustness of measures used to monitor hematologic safety, Stein Gold reaffirmed, “No clinically meaningful changes in hematologic parameters were observed, which underscores the reliability of the monitoring methods employed in the study. These measures included tracking hemoglobin, platelet, and neutrophil counts at specified intervals to ensure comprehensive safety evaluation.”

Plasma Concentrations in Pediatric vs. Adult Populations

On the comparison of plasma concentrations of ruxolitinib cream between pediatric and adult populations, Stein Gold noted, “Mean plasma concentrations of ruxolitinib cream at weeks 2 or 4 and at week 8 were below a threshold associated with bone marrow myelosuppression (281 nM) with both strengths of ruxolitinib cream across age subgroups. In the adult and adolescent trial, we saw similar results with the mean plasma concentration well below the level necessary for systemic JAK inhibition.”

Unexpected Findings or Adverse Events

Stein Gold reported no unexpected findings or adverse events related to hematologic safety during the 8-week treatment period. “Safety was consistent across age groups and disease severity,” she confirmed, highlighting the overall safety profile of ruxolitinib cream in the pediatric population.

Implications for Long-Term Use

Considering the implications of these results for the long-term use of ruxolitinib cream in pediatric patients, Stein Gold shared, “We have a long-term (52 weeks) tolerability, safety, systemic exposure, disease control, and impact on PROs of 1.5% ruxolitinib cream in children aged 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.”

Final Thoughts

In conclusion, Stein Gold expressed her excitement about the research, stating, “I am excited about the safety and efficacy of ruxolitinib cream in this younger population as it will be an important tool in our treatment armamentarium.” The findings from the TRuE-AD3 Phase 3 study underscore the potential of ruxolitinib cream as a safe and effective treatment option for children with mild to moderate atopic dermatitis, offering hope for better disease management and improved quality of life for these young patients.

Reference

Stein Gold L. Hematologic laboratory safety of ruxolitinib cream in children aged 2 to 11 years with mild to moderate atopic dermatitis: results from a randomized, double-blind, vehicle-controlled phase 3 study (TRuE-AD3). Data presented at: 2024 Society for Pediatric Dermatology Meeting; July 11-14, 2024; Toronto, Canada.