Delgocitinib Reduces Work and Activity Burden in CHE

Chronic hand eczema (CHE) is often characterized clinically by erythema, vesicles, scaling, hyperkeratosis, and fissures. For patients, however, the disease is experienced as something far more pervasive: persistent itch and pain, disrupted sleep, difficulty gripping objects, embarrassment about visible lesions, and, in many cases, impaired ability to work. Moderate to severe CHE has been shown to carry a quality-of-life burden comparable to psoriasis, atopic dermatitis, and even some chronic nondermatologic illnesses.¹

Yet therapeutic options remain limited. High-potency topical corticosteroids are standard of care but may be associated with skin atrophy, barrier impairment, and other adverse effects with prolonged use. Oral alitretinoin is approved in some regions for severe disease refractory to topical corticosteroids, but its use requires laboratory monitoring and strict pregnancy prevention measures.² With this in mind, researchers behind a recent analysis recognized that new topical agents with improved efficacy and tolerability are needed.

A pooled analysis of 2 phase 3 trials—DELTA 1 (NCT04871711) and DELTA 2 (NCT04872101)—provides detailed insight into the patient-reported impact of delgocitinib cream 20 mg/g, a first-in-class topical pan–Janus kinase (JAK) inhibitor, in adults with moderate to severe CHE.³

Trial Design and Baseline Burden

DELTA 1 and DELTA 2 were randomized, double-blind, vehicle-controlled, multicenter studies of identical design. Adults with moderate (Investigator Global Assessment CHE score of 3 [IGA-CHE 3]) or severe (IGA-CHE 4) disease and inadequate response to topical corticosteroids, or for whom corticosteroids were medically inadvisable, were randomly assigned 2:1 to twice-daily delgocitinib cream 20 mg/g or cream vehicle for 16 weeks.

Across both trials, 639 patients received delgocitinib and 321 received vehicle. The population was predominantly women (64%) and White (90%), with a mean disease duration of approximately 10 years. Most had moderate disease at baseline (72%).

Patient-reported outcomes (PROs) at baseline underscored the depth of impairment. The mean EuroQol 5-Dimension (EQ-5D) index score was 0.65, a level comparable to that reported in more generalized inflammatory dermatoses. The mean Dermatology Life Quality Index (DLQI) was 12.4, indicating a “very large” effect on quality of life.

Three instruments were used to assess health-related quality of life (HRQoL): the 5-level EQ-5D (generic health status), the DLQI (dermatology-specific), and the Hand Eczema Impact Scale (HEIS), including its Proximal Daily Activity Limitations (PDAL) and Embarrassment domains.

Early and Sustained Improvements in HRQoL

Improvements with delgocitinib were evident quickly. For the EQ-5D index, statistically significant separation from vehicle was observed as early as week 1 (P = .022), with continued divergence through week 16. At week 16, the least squares mean change from baseline was 0.17 with delgocitinib vs 0.06 with vehicle (treatment difference, 0.11; 95% CI, 0.08-0.13; P < .001).

Benefits were seen across all 5 EQ-5D domains, including pain/discomfort and anxiety/depression. Although mobility showed smaller gains—as might be expected in a hand-limited condition—the overall pattern suggested broad improvement in perceived health status.

The DLQI findings were similarly robust. At week 16, the mean reduction from baseline was −7.3 with delgocitinib compared with −3.5 with vehicle (treatment difference, −3.8; 95% CI, −4.5 to –3.0; P < .001). Clinically meaningful improvement, defined as a 4-point or greater reduction, was achieved by 73.3% of patients receiving delgocitinib vs 47.8% receiving vehicle (P < .001).

Importantly, the median time to DLQI response was shorter with delgocitinib (21 days) than with vehicle (30 days). Patients treated with delgocitinib also spent substantially more time in a response state over the 16-week period (80.5 days vs 53.2 days; P < .001).

Improvements spanned all 10 DLQI items, with particularly notable effects on work and study, daily activities, leisure, and skin-related embarrassment or self-consciousness—domains that resonate strongly with the lived experience of CHE.

Capturing the CHE-Specific Burden

The HEIS, developed specifically for CHE, offered a more granular look at disease impact. At week 16, mean HEIS improvement was −1.46 with delgocitinib vs −0.73 with vehicle (treatment difference, −0.72; P < .001). A clinically meaningful response (≥ 1.3-point reduction) was achieved by 62.3% of patients treated with delgocitinib compared with 33.0% receiving vehicle (P < .001).

Median time to HEIS response was 21 days with delgocitinib vs 84 days with vehicle. Patients treated with delgocitinib also spent significantly more time in response (61.9 days vs 33.4 days; P < .001).

Parallel improvements were observed in the HEIS PDAL domain—reflecting limitations in activities such as washing and housework—and in the Embarrassment domain. For the latter, median time to response was 31 days with delgocitinib compared with 163 days with vehicle.

Interpreting the Findings

Notably, clinically meaningful PRO improvements were observed even in the vehicle group, with nearly half achieving a DLQI response at week 16. The specially formulated vehicle and the structured care inherent to trial participation likely contributed to these gains. However, across all instruments, the magnitude, speed, and durability of response consistently favored delgocitinib.

An additional observation was that improvements in PROs were sometimes seen even in the absence of a change in IGA score, underscoring the importance of incorporating PROs into clinical evaluation of CHE.

Looking Ahead

The pooled DELTA 1 and DELTA 2 data demonstrate that twice-daily delgocitinib cream 20 mg/g significantly improves generic, dermatology-specific, and CHE-specific quality-of-life measures in adults with moderate to severe disease. Improvements were rapid, clinically meaningful, and sustained over 16 weeks.

Limitations include the predominantly White study population and relatively short duration. Longer-term data are anticipated from ongoing extension studies.

For clinicians, these findings reinforce 2 key points: the profound multidimensional burden of CHE and the potential for targeted topical JAK inhibition to meaningfully address not only clinical signs but also the daily functional and psychosocial impact that patients experience.

References

1. Buhl T, Bauer A, Ehst BD, et al. Health-related quality of life in chronic hand eczema in a phase 2b trial of delgocitinib cream. Dermatol Ther (Heidelb). 2025;15(5):1181-1193. doi:10.1007/s13555-025-01384-4
2. Ghezzi G, Falcidia C, Paolino G, et al. Chronic hand eczema (CHE): a narrative review. Dermatol Ther (Heidelb). 2025;15(4):771-795. doi:10.1007/s13555-025-01365-7
3. Bauer A, Guenther L, Woolf R, et al. Effect of delgocitinib cream on health-related quality of life in patients with moderate to severe chronic hand eczema. Contact Dermatitis. Published online March 3, 2026. doi:10.1111/cod.70114