Topical Delgocitinib Improves Chronic Hand Eczema Outcomes Across All Trial Timepoints

For people living with chronic hand eczema (CHE), a condition that can make everyday tasks painful and limit their ability to work, a new analysis of randomized trial data reinforces that the topical pan-Janus kinase (JAK) inhibitor delgocitinib offers meaningful benefits over placebo across multiple efficacy end points, with a favorable safety profile.

A systematic review and meta-analysis published in Experimental Dermatology pooled data from 4 randomized controlled trials (RCTs) involving 1154 patients to assess the efficacy and safety of topical delgocitinib 20 to 30 mg/g compared with placebo in adults with CHE.¹ Of the total patient population, 752 received delgocitinib and 402 received placebo. Participants were predominantly female (65%), and ages ranged from approximately 41 to 48 years across trials. Most patients had moderate disease, with 69.2% classified as moderate and 27.2% classified as severe based on Investigator's Global Assessment (IGA) or Physician's Global Assessment (PGA) scores.

Why a Meta-Analysis Was Needed for Chronic Hand Eczema Treatment

CHE is an inflammatory skin disease of the hands and/or wrists characterized by persistent or recurrent episodes lasting more than 3 months or relapsing at least twice per year. Its estimated prevalence in the general population is approximately 4.7%, with higher rates among women, employed individuals, and urban residents. Beyond its clinical burden, CHE carries significant occupational and psychological consequences.

The consequences of CHE extend well beyond the skin. A 2025 narrative review published in Acta Dermato-Venereologica documented the breadth of physical, psychosocial, occupational, and socioeconomic burdens faced by people living with CHE, noting that the condition has a median duration of 11 to 16 years and may flare repeatedly over that span.² Itch and skin pain, the same patient-reported symptoms assessed in the current meta-analysis by de Moraes-Souza and colleagues, were identified among the most common and burdensome features of the disease. The socioeconomic toll is also substantial: Annual per-patient costs in Europe have been estimated at between approximately €1800 and €7700, driven by both direct medical costs and indirect costs such as absenteeism and lost productivity. In a survey of patients with CHE from the Danish Skin Cohort, 84.8% reported at least 1 adverse event from topical corticosteroid use, and 76% indicated a preference for a nonsteroidal treatment option, underscoring the unmet need that delgocitinib's approval was designed to address.

Topical corticosteroids have long been the standard of care, but their prolonged use is associated with adverse effects, including skin atrophy and tachyphylaxis.¹ Delgocitinib, a pan-JAK inhibitor targeting JAK1, JAK2, JAK3, and tyrosine kinase 2, was approved by the European Medicines Agency in 2024 and the FDA in 2025, representing the first topical therapy developed specifically for CHE. While individual trial data existed, no comprehensive meta-analysis had synthesized findings across all available RCTs with detailed adverse event (AE) analysis.

Delgocitinib Demonstrated Significantly Higher Treatment Success Rates at Week 16

The primary outcome was treatment success at week 16, defined as achieving clear or almost clear skin with at least a 2-point improvement on IGA or PGA. Pooled data from 3 RCTs, DELTA 1 (NCT04871711), DELTA 2 (NCT04872101), and Worm 2022, showed that significantly more patients receiving delgocitinib achieved this threshold compared with those receiving placebo (25.3% vs 8.4%; relative risk [RR], 3.17; 95% CI, 1.78-5.65; P < .0001). The absolute risk difference was 16.9%, corresponding to a number needed to treat of 6 (95% CI, 3-16).

Treatment success was also significantly greater in the delgocitinib group at week 4 (15.1% vs 6.2%; RR, 2.32; 95% CI, 1.53-3.52; P < .0001) and week 8 (28.7% vs 9.3%; RR, 2.93; 95% CI, 1.97-4.36; P < .00001), with all 4 trials contributing to those pooled analyses. Patients treated with delgocitinib also experienced significantly greater reductions in Hand Eczema Symptom Diary (HESD) itch scores (mean difference [MD], –1.80; 95% CI, –2.17 to –1.44; P < .00001) and pain scores (MD, –1.80; 95% CI, –2.15 to –1.45; P < .00001) compared with those receiving placebo.

The authors noted the clinical significance of the early response signal: "Importantly, the early statistical difference at week 4 highlights the potential impact on treatment adherence, as patients are more likely to persist with therapy when improvement is observed early in the treatment course."

Adverse Event Rates Were Comparable Between Treatment Groups

Safety endpoints were consistent across all four trials. Overall AE rates did not differ significantly between groups (48.2% vs 49.0%; RR, 1.03; 95% CI, 0.89-1.18; P = .74). The most commonly reported AEs included nasopharyngitis, eczema or hand dermatitis, headache, and COVID-19. Treatment-related AEs and serious AEs similarly showed no statistically significant differences between groups. Notably, AEs leading to treatment discontinuation were significantly lower among patients receiving delgocitinib compared with those receiving placebo (0.7% vs 4.2%; RR, 0.21; 95% CI, 0.08-0.55; P = .002).

Limitations Include Short Follow-Up and Lack of Active Comparator

The authors acknowledged several limitations. Efficacy and safety data were available only through week 16, though the open-label extension DELTA 3 trial (NCT04949841) provides supporting evidence that therapeutic effects are sustained for up to 52 weeks without new safety signals. The meta-analysis also compared delgocitinib with placebo rather than an active treatment such as topical corticosteroids, limiting its applicability to real-world clinical decision-making. Moderate heterogeneity was observed for the primary efficacy outcome, largely attributed to differences in baseline disease severity and CHE phenotype distribution across trials. Importantly, leave-one-out sensitivity analyses confirmed that these sources of variability did not materially alter the pooled estimates. Additionally, the strict IGA 0–1 threshold for treatment success may have contributed to the relatively modest absolute response rates observed in both groups.

References

1. de Moraes-Souza R, Pilau Bornia MJ, Chahine Chater R, et al. Efficacy and safety of topical delgocitinib for chronic hand eczema: a systematic review and meta-analysis of randomized controlled trials. Exp Dermatol. 2026;35:e70242. doi:10.1111/exd.70242
2. Agner T, Bauer A, Barbarot S, et al. Chronic hand eczema, real world, and patient centricity: a narrative review. Acta Derm Venereol. 2025;105:42596. doi:10.2340/actadv.v105.42596