Efficacy and Safety of Topical Delgocitinib in Patients With Chronic Hand Eczema

Data From a Randomized, Double-blind, Vehicle-controlled Phase IIa Study

M. Worm; A. Bauer; P. Elsner; V. Mahler; S. Molin; T.S.S. Nielsen

Disclosures

The British Journal of Dermatology. 2020;182(5):1103-1110. 

In This Article

Abstract and Introduction

Abstract

Background: Management of chronic hand eczema (CHE) remains a challenge; effective topical treatment is limited to corticosteroids.

Objectives: To assess the efficacy and safety of a novel, pan-Janus kinase inhibitor (delgocitinib) in patients with CHE.

Methods: In this randomized, double-blind, phase IIa study, patients with CHE received delgocitinib ointment 30 mg g−1 or vehicle ointment for 8 weeks. The primary end point was the proportion of patients achieving treatment success ['clear'/'almost clear' skin with ≥ 2-point improvement in the Physician's Global Assessment of disease severity (PGA)] at week 8. Secondary end points included Hand Eczema Severity Index (HECSI) score changes and the proportion of patients achieving treatment success on the Patient's Global Assessment of disease severity (PaGA).

Results: Ninety-one patients were randomized. More patients receiving delgocitinib (46%) than vehicle (15%) [odds ratio 4·89, 95% confidence interval (CI) 1·49–16·09; P = 0·009] achieved treatment success (PGA). Adjusted mean HECSI score at week 8 was lower with delgocitinib (13·0) than with vehicle (25·8) (adjusted mean difference −12·88, 95% CI −21·47 to −4·30; P = 0·003). More patients receiving delgocitinib than vehicle achieved treatment success by PaGA, but this did not reach statistical significance. The incidence of adverse events was similar with delgocitinib and vehicle; none led to discontinuation of delgocitinib.

Conclusions: Delgocitinib ointment was efficacious and well tolerated. As a plateau of efficacy was not observed, a longer treatment period may lead to increased efficacy. Further clinical studies are warranted to confirm these findings in patients with CHE.

Introduction

Hand eczema is a chronic inflammatory skin disease,[1] with varying and potentially interlinked aetiology, such as irritant or allergic contact dermatitis or atopic hand dermatitis. It is common in the general population, with an overall reported 1-year prevalence of around 10%.[2–4] Hand eczema is considered chronic (CHE) if it lasts at least 3 months or relapses twice or more in 1 year.[4] Common signs of CHE include erythema, oedema, blistering, thickening and fissures, while itch and pain are symptoms experienced by many patients.[5,6] CHE has a marked negative impact on patients' medical well-being and quality of life (QoL);[7–11] in particular, itch can have a negative impact on QoL.[8,12] Although the molecular mechanisms underlying CHE are not fully understood, a large panel of cytokine-mediated signalling cascades have been identified as part of the pathophysiology, including T-helper 2 (Th2) [interleukin (IL)-4, IL-13], Th22 (IL-22), Th17 (IL-17), Th1 (interferon-γ) and the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway.[13–15]

Emollients and topical corticosteroids are the mainstay of CHE treatment.[4,16] In addition, many patients with CHE do not receive adequate treatment,[6] which may be the result of misperceptions about CHE or to treatment-specific concerns.[4] For example, it is recommended that corticosteroids should not be used for > 6 weeks because of side-effects, such as skin atrophy and barrier impairment.[4,17] Also, systemic treatments for CHE are limited, with alitretinoin currently being the only approved treatment with an indication for CHE in Europe.

Delgocitinib is a novel, pan-JAK inhibitor specific for JAK1, JAK2, JAK3 and tyrosine kinase 2.[18] It blocks several cytokine-mediated signalling cascades, thereby inhibiting inflammation, and might, therefore, be a suitable therapeutic agent for topical use in CHE. The aim of this study was to evaluate the efficacy and safety of delgocitinib ointment over 8 weeks of treatment in adult patients with CHE refractory to topically applied steroids.

processing....