Delgocitinib shows promise as topical therapy for chronic hand eczema

The DELTA 1 trial on topical treatment with the pan-JAK inhibitor delgocitinib demonstrated significant improvement in chronic hand eczema at week 16. More patients with chronic hand eczema achieved clear or almost clear skin in the Investigator’s Global Assessment (IGA) with delgocitinib compared with a vehicle cream.

Chronic hand eczema (CHE) is a highly prevalent, chronic, inflammatory dermatosis that causes a high burden of disease and is often challenging to treat. Currently, approved topical treatments specific for CHE are lacking [1]. After encouraging results on topical delgocitinib for CHE in a phase 2b dose-ranging study, the development further advanced to the phase 3 DELTA 1 trial (NCT04871711) [2]. Included were adults with moderate-to-severe CHE represented by an IGA score of 3 or 4. IGA-CHE scores includes 0 (clear), 1 (almost clear, with little or no disease left), 2 (mild), 3 (moderate), and 4 (severe). As per inclusion criteria, their disease had lasted more than 3 months, and the patients had contraindications for topical steroids.

The study randomised 487 patients 2:1 to delgocitinib cream (20 mg/g; twice daily) or vehicle. The primary endpoint, which was considered a “very high bar” according to Dr Robert Bissonnette (Innovaderm Research, Canada), consisted of a 2-grade improvement with a final IGA 0/1 at week 16.

The mean age of the DELTA 1 cohort was 44 years, with a median age of 32 years at the onset of CHE. One-third of the participants had severe CHE and the median Dermatology Life Quality Index (DLQI) was 12.0, which stands for a very high impact of the disease on the quality of life.

At week 16, 19.7% of the 325 participants in the active-treatment arm reached the IGA-CHE score of clear or almost clear skin, which was significantly more than in the vehicle arm (9.9%; P=0.006). A 75% improvement in the hand eczema severity index (HECSI) was achieved by 49.2% versus 23.5% and a 90% improvement in HECSI by 29.5% versus 12.3%, for delgocitinib and vehicle cream respectively (P<0.001 for both comparisons in favour of delgocitinib). A ≥4-point improvement in DLQI was observed in 74.4% in the delgocitinib arm versus 50.0% in the vehicle arm (P<0.001).

The safety assessment revealed higher rates of adverse events in the vehicle arm (50.6% vs 45.2%) with similar proportions of serious adverse events (1.9% vs 1.8%). COVID-19 infections and nasopharyngitis were the most common adverse events with comparable rates between the treatment arms. Adverse events of special interest, such as thromboembolic events, did not occur.

In his conclusion, Dr Bissonnette emphasised that delgocitinib cream significantly improved patient-reported and clinician-reported efficacy outcomes compared with vehicle treatment in this difficult-to-treat patient population.

1. Bauer A, et al. Contact Dermatitis. 2023 Apr 10. DOI: 10.1111/cod.14303.
2. Elsner P, Agner T. J Eur Acad Dermatol Venereol. 2020; 34:13–21.
3. Bissonnette R. Efficacy and safety of delgocitinib cream in adults with moderate-to-severe chronic hand eczema: results of the phase 3 DELTA 1 trial. S025, AAD 2023 Annual Meeting, 17–21 March, New Orleans, USA.

Posted on 15 May, 202327 March, 2024