715 - Ruxolitinib: what’s stopping us?
Authors: Truong Tiffany N , Chase Nicole M 
Published: August 2024

Abstract

Background
Atopic dermatitis (AD) is a chronic inflammatory skin disorder and a leading contributor to skin-related disability.1 Management of AD involves a step-up approach utilizing emollients, topical medications, UV phototherapy, systemic corticosteroids, oral immunomodulators, biologics, and small molecules. Dupilumab is a monoclonal antibody that downregulates Th2 inflammation via blockade of IL-4 and IL-13 signaling.2 Dupilumab is FDA-approved for treatment of moderate to severe atopic dermatitis in patients 6 months of age and older.3 Despite data that a sizable number of patients on dupilumab can achieve an IGA score of 0 to 1 after 16 weeks of therapy, there remains a population of AD patients who fail to achieve this outcome – for this reason, consideration of combination therapies is warranted.4 Topical ruxolitinib is a JAK1/2 inhibitor that is FDA-approved for use in patients 12 years and older for short-term, non-continuous treatment of mild to moderate atopic dermatitis. Blockade of signal transduction via JAK1/2 abrogates STAT-mediated transcription of pro-inflammatory Th2 cytokines.5 The package insert for ruxolitinib states, “Use … in combination with therapeutic biologics, other JAK inhibitors or potent immunosuppressants such as azathioprine or cyclosporine is not recommended.”5 This concern has not been substantiated by randomized, controlled trials. In practice, we have opted to engage patients with persistent AD of &lt;5% BSA in shared decision making prior to offering topical ruxolitinib as an adjunct therapy; many of these patients are ultimately able to achieve clear or almost clear skin (IGA 0/1).

Objective
To describe a population of patients receiving dupilumab for AD who use or have used concomitant topical ruxolitinib and describe their characteristics.

Methods
We identified 9 patients currently on dupilumab plus topical ruxolitinib for AD. We summarized data on age, gender, location of persistent AD, identifiable triggers, and response to additive treatment with ruxolitinib.

Results
Eight patients initially received topical ruxolitinib as a sample; one patient received prescription topical ruxolitinib. Four patients reported subjective improvement, ranging between “significant, but not complete relief; cheeks now just forehead”, “decreased itchiness”, “helpful, very beneficial”, to “well controlled, few remaining patches on hands and arms.” An additional four patients had not yet returned for follow-up after initiating treatment with topical ruxolitinib. There were no reports of adverse effects, but barriers to continuing topical ruxolitinib included cost, insurance non-coverage, and being told not to use concomitant dupilumab and ruxolitinib. Of the patients who followed up, the shortest duration of use was two weeks; this was due to cost and being told not to use dupilumab while on a JAK inhibitor or other biologics.

Conclusions
For some patients with persistent AD despite dupilumab therapy, limited use of topical ruxolitinib may be of high utility and low risk. However, barriers to use include lack of randomized controlled trials, insurance non-coverage, and cost. Limitations of this study include the observational nature and a small sample size. Future directions include formal placebo-controlled studies with laboratory parameters and validated scoring metrics for AD response to therapy.