Current emerging and investigational drugs for the treatment of chronic hand eczema

ABSTRACT

Introduction

Chronic hand eczema (CHE) is a highly prevalent, burdensome condition associated with functional impairment. Currently, topical therapeutics are the mainstay of CHE management. However, many cases are refractory to existing topical therapeutics, and the few existing systemic options are often limited in efficacy and by their side effect profiles.

Areas covered

Following a brief overview of CHE pathogenesis and existing treatments, this review will outline the mechanisms and available data on emerging and investigational drugs currently being studied in clinical trials for the treatment of CHE.

Expert opinion

Immunomodulatory drugs such as topical and systemic JAK inhibitors and Th2-targeting antibodies such as dupilumab are currently under investigation for CHE treatment, with early promise. Management of CHE will likely move toward more targeted treatments through clinical trials and away from broad immunosuppressants such as cyclosporine and methotrexate, which have previously been investigated for CHE and have more side effects. In coming years, CHE patients may benefit from a wider range of both topical and systemic therapeutics that target immune pathways relevant to the various CHE subtypes.

KEYWORDS:

• AFX5931
• chronic hand eczema
• delgocitinib
• dupilumab
• gusacitinib
• roflumilast
• ruxolitinib

Article highlights

• New topical therapies under investigation in clinical trials for CHE include the pan-JAK inhibitor delgocitinib, the JAK1/JAK2 inhibitor ruxolitinib, the PDE-4 inhibitor roflumilast, and the CCL2/CCL5 inhibitor AFX5931.

• Two clinical trials investigating topical delgocitinib for CHE treatment have been completed, showing early promise for topical treatment of mild-to-severe CHE with minimal adverse effects. Phase 3 clinical trials for delgocitinib (DELTA1, DELTA2, and DELTA3) are ongoing.

• Topical ruxolitinib is being evaluated as a potential treatment for CHE in two ongoing clinical trials. Studies on roflumilast and AFX5931 have been completed, but results have not yet been published.

• New systemic therapies that are under investigation for CHE include dupilumab and gusacitinib. Two phase 2 clinical trials are still ongoing for dupilumab, but case reports and observational studies have pointed toward its potential efficacy. Frontline results for a phase 2 study on gusacitinib suggest favorable outcomes and safety profile.

Declaration of interest

Emma Guttman-Yassky is an employee of Mount Sinai and has received research funds (grants paid to the institution) from: AbbVie, Almirall, Amgen, AnaptysBio, Asana Biosciences, AstraZeneca, Boehringer-Ingelheim, Cara Therapeutics, Celgene, Eli Lilly, Galderma, Glenmark/Ichnos Sciences, Innovaderm, Janssen, KAO, Kiniksa, Kyowa Kirin, Leo Pharma, Novan, Novartis, Pfizer, Ralexar, Regeneron Pharmaceuticals, UCB. She is also a consultant for:

AbbVie, Almirall, Amgen, Arena, Asana Biosciences, Aslan Pharmaceuticals, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Celgene, Connect Pharma, Eli Lilly, EMD Serono, Evidera, Galderma, Ichnos Sciences, Incyte, Janssen Biotech, Kyowa Kirin, Leo Pharma, Pandion Therapeutics, Pfizer, RAPT Therapeutics, Regeneron Pharmaceuticals, Inc., Sanofi, SATO Pharmaceutical, Siolta Therapeutics, Target Pharma Solutions, UCB, Ventyx Biosciences. Benjamin Ungar is an employee of Mount Sinai and has received research funds (grants paid to the institution) from: Pfizer. He is also a consultant for Arcutis Biotherapeutics. The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.