Evaluating topical JAK inhibitors as a treatment option for atopic dermatitis

ABSTRACT

Introduction

Atopic dermatitis (AD) is a chronic, inflammatory skin condition mediated by cytokines that utilize the Janus Kinase/Signal Transducer and Activator of Transcription (JAK-STAT) signaling cascade. Topical JAK inhibitors are an emerging alternative in the treatment of AD.

Areas Covered

This expert review presents an overview of the underlying molecular pathophysiology of AD, current standards of care, and evaluation of the efficacy and safety of topical JAK inhibitors. A PubMed database search was utilized with a focus on the evidence from double-blind, randomized Phase I, II, and III clinical trials published between January 2015 and July 2021.

Expert Opinion

Current topical therapies for AD are efficacious but limited by their adverse side effects. Long-term topical corticosteroid use leads to loss of pigmentation, striae, and skin atrophy. Patients may be concerned about topical calcineurin inhibitors’ black box warning of increased risk of malignancy. Topical crisaborole, a phosphodiesterase four inhibitor, is limited by application site burning. Topical ruxolitinib is a JAK inhibitor comparable to triamcinolone in efficacy without the adverse effects seen with long-term topical corticosteroid use. Although topical JAK inhibitors have promising efficacy and safety profiles, poor medication adherence common to topical treatments may limit their utility in a clinical setting.

KEYWORDS:

• Delgocitinib
• dermatology
• Eczema Area and Severity Index
• efficacy
• safety
• pruritus
• ruxolitinib
• skin
• tofacitinib

Article highlights

• Atopic dermatitis is one of the most prevalent skin diseases caused by an interplay of genetic susceptibility, epidermal barrier dysfunction, and immune system dysregulation.

• Topical ruxolitinib is a JAK inhibitor that selectively targets JAK1 and JAK2 with rapid and sustained antipruritic and anti-inflammatory effects that is comparable to triamcinolone in efficacy and can be utilized for longer durations with no skin atrophy, striae, or loss of pigmentation.

• Topical delgocitinib is a pan-JAK inhibitor effective in the treatment of AD in children and adults, improving Numerical Rating Scale pruritus scores, Investigator’s Global Assessment responses, and other efficacy parameters.

• Topical delgocitinib is a potential novel treatment option for irritant contact and non-irritant contact chronic hand dermatitis as it improves Investigator’s Global Assessment scores and Hand Eczema Severity Index scores from baseline in a dose-dependent manner.

• Topical tofacitinib is a JAK1 and JAK3 inhibitor that improves AD severity in adults with improvement in Eczema Area and Severity Index total scores, Physician Global Assessment scores, and reduction of pruritus.

• The most common treatment-related adverse event in patients treated with topical delgocitinib over a 52-week period was application site folliculitis, and the most-common treatment emergent adverse event was nasopharyngitis.

Declaration of interests

S Feldman has received research, speaking and/or consulting support from a variety of companies including Galderma, GSK/Stiefel, Almirall, Leo Pharma, Baxter, Boeringer Ingelheim, Mylan, Celgene, Pfizer, Valeant, Taro, Abbvie, Cosmederm, Anacor, Astellas, Janssen, Lilly, Merck, Merz, Novartis, Regeneron, Sanofi, Novan, Parion, Qurient, National Biological Corporation, Caremark, Advance Medical, Sun Pharma, Suncare Research, Informa, UpToDate, Alvotech, vTv, Samsung, BMS, Amgen, Arena, Helsinn, UCB, Arcutis, Dermavant, Forte and National Psoriasis Foundation. He is founder and majority owner of www.DrScore.com and founder and part owner of Causa Research, a company dedicated to enhancing patients’ adherence to treatment. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper is not funded.