Re-Framing The Safety of JAK Inhibitors: A Maximum-Use Trial of Topical Ruxolitinib in Children with Eczema

Original Article: A Maximum-Use Trial of Ruxolitinib Cream in Children Aged 2-11 Years with Moderate to Severe Atopic Dermatitis

What are the key takeaways of this article?

Topical Ruxolitinib is a JAK1/2 inhibitor that is effective in treating nonsegmental vitiligo and mild-to-moderate atopic dermatitis (AD). In Canada, it has been approved for these conditions in adult and pediatric patients 12 years of age and older. However, little research has investigated its use in younger children. In this recent single-arm maximum-use study, Gold et al. investigated the safety, tolerability, pharmacokinetics, efficacy, and quality of life impact of topical ruxolitinib cream in children aged 2-11 years with moderate-to-severe AD.

A maximum-use trial aims to evaluate the safety of the maximum exposure of a topical investigational product in an appropriate patient population. Since the safety and tolerability of oral JAK inhibitors have been topics of discussion, particularly in children, this study’s outcomes will provide valuable insights into the risks associated with topical JAK inhibitors as an alternative to topical steroids in the treatment of AD.

This open-label maximum-use trial included 29 patients aged 2-11 years, diagnosed with moderate-to-severe AD (Investigator’s Global Assessment (IGA) of 3 or 4 and Body Surface Area (BSA) involvement of over 35%) for a duration of over 3 months. The treatment period was 8 weeks in total: for the first 4 weeks, patients applied 1.5% Ruxolitinib cream BID to all AD lesions identified at baseline, and then for the next 4 weeks, cream was applied to active lesions only. At 8 weeks, patients who responded to treatment were eligible to participate in the long-term study extension up to 52 weeks using 1.5% Ruxolitinib cream BID as needed.

Ruxolitinib was well-tolerated with treatment-emergent adverse events reported in 31% of patients (n=9/29). There were no adverse events of special interest (i.e., no serious infection, malignancies, major adverse cardiovascular events, or thromboses) during the study period. Pharmacokinetics was evaluated in 26 patients, demonstrating that the mean Ruxolitinib steady-state concentration was below the half-maximal concentration of JAK-mediated myelosuppression in adults. Thus, even at maximal use, topical Ruxolitinib had a low risk of myelosuppression. In terms of efficacy, the mean affected BSA decreased from 58% at baseline to 11.4% at week 4, to 10.2% at week 8, to 2.2% at week 52. EASI-75 was achieved in 76.9% and 84% of patients at week 4 and week 8, respectively.

Limitations of this study include its small sample size and open-label design, however, uncontrolled treatment groups are appropriate for a maximum-use trial. This study’s strengths included recruitment of patients with more extensive disease and completing long-term follow-up.

In summary, this study adds to the growing body of evidence to support the efficacy and safety of 1.5% Ruxolitinib cream in the treatment of AD. Furthermore, the results of this maximum-use trial support the safety of 1.5% Ruxolitinib cream in children aged 2-11 years, an age group for which there exist limited treatment options in AD. Topical Ruxolitinib may be considered an effective non-steroidal alternative to systemic therapies in children with severe disease.

Publication Date: March 21, 2025

Reference: Stein Gold L, Bissonnette R, Forman S, Zaenglein A, Kuo Y, Angel B, Chen X, Kallender H, Paller AS. A Maximum-Use Trial of Ruxolitinib Cream in Children Aged 2-11 Years with Moderate to Severe Atopic Dermatitis. Am J Clin Dermatol. 2025 Jan 6. doi: 10.1007/s40257-024-00909-5. Epub ahead of print. PMID: 39760983.

Summary By: Nicholas Chiang