Topical Delgocitinib Rivals Dupilumab for Hand Eczema, but Adherence Is Key

Fissured palms and cracked knuckles can turn typing, dishwashing, and handshakes into daily trials, and until recently, injectable dupilumab was the only advanced option once topical corticosteroids failed. An indirect comparison of the drugs' pivotal trials found that a topical alternative, delgocitinib cream, performed just as well.¹

Chronic Hand Eczema's Burden Fuels the Search for Alternatives

Chronic hand eczema affects a substantial share of the general population and often persists for years.²

A Danish population survey found a 1-year prevalence of 13.3%, of which 82.6% met criteria for chronic disease and 35.1% were moderate to severe; individuals with hand eczema also reported worse overall health and more sick leave than those without the condition, underscoring how a condition often dismissed as cosmetic carries real occupational and psychological costs.

Dupilumab, an injectable interleukin-4/13 inhibitor, has been revolutionary for atopic dermatitis that does not respond to topical therapies, but Janus kinase nhibitors such as delgocitinib now offer a topical alternative for chronic hand eczema.¹

Delgocitinib cream was approved by the FDA in July 2025 as the first drug specifically indicated for adults with chronic hand eczema who have an inadequate response to topical corticosteroids or for whom corticosteroids are medically inadvisable. With injectable and topical options both available, the letter's authors set out to compare how the 2 actually stack up.

DELTA and LIBERTY-AD-HAFT Trials Diverged in Design

No head-to-head trial has compared delgocitinib with dupilumab for chronic hand eczema, so the authors relied on a matching-adjusted indirect comparison (MAIC) built from the drugs' respective phase 3 programs: DELTA 1 (NCT04871711) and DELTA 2 (NCT04872101), which together randomized roughly 960 adults with moderate to severe chronic hand eczema to delgocitinib cream or vehicle, and LIBERTY-AD-HAFT (NCT04417894), which randomized 133 adults and adolescents with moderate to severe atopic hand and foot dermatitis to dupilumab or placebo. An anchored MAIC is a reasonable substitute when direct comparisons are unavailable, but the authors cautioned that it was not possible to control for all effect modifiers and prognostic factors between the trials.

The 2 trial populations were not identical. LIBERTY-AD-HAFT enrolled patients with generalized atopic dermatitis beyond the hands and feet, while DELTA 1 and DELTA 2 excluded patients who needed treatment for atopic dermatitis outside the hands and feet. The trials also used different severity scales: DELTA's Investigator's Global Assessment (IGA)-Chronic Hand Eczema measure required an "almost clear" rating to show only barely perceptible erythema with no lichenification, scaling, vesiculation, edema, or fissures, while LIBERTY-AD-HAFT's Hand and Foot-IGA scale allowed residual erythema, lichenification, scaling, or edema within its "almost clear" category and permitted scores to step down when lesions were limited in extent.

Delgocitinib Matched Dupilumab Across Efficacy End Points

After 16 weeks, the 2 treatments produced comparable results on IGA 0/1 response, Hand Eczema Severity Index (HECSI-75/90) response, and percentage improvement from baseline. Despite being held to the stricter IGA-chronic hand eczema criteria, delgocitinib was numerically better than dupilumab on every efficacy end point, although the difference did not reach statistical significance.

“The efficacy outcomes of this study contradict the assumption that systemic medications are more efficacious than topical medications for patients with hand dermatitis who have failed topical corticosteroids,” the authors wrote. They suggested the topical option could appeal to patients who fear injections or want to avoid systemic immunosuppression, and that because dupilumab remains costly for uninsured patients, delgocitinib—while still expensive—might offer a less costly path to treatment, potentially shifting prescribing patterns in resource-constrained practices that lack ready access to dupilumab.

Adherence Gaps May Temper Real-World Performance

The comparable trial results may not translate directly into practice, the authors cautioned, because adherence to topical treatment for inflammatory skin disease tends to be markedly worse than adherence to biologics, and hand dermatitis is no exception. Delgocitinib also carries warnings about serious infection, nonmelanoma skin cancer, and potentially higher rates of all-cause mortality, including cardiovascular death, pulmonary embolism, and malignancy, that patients may find alarming enough to affect how consistently they use it.

DELTA 1 and DELTA 2 built in structural supports for adherence that are unlikely to be replicated in routine care: supervised first application at the trial center; visits at weeks 1, 2, 4, 8, 12, and 16; and daily electronic symptom diaries. Patients who reach delgocitinib after already failing daily topical corticosteroids—itself sometimes a marker of poor adherence—may be especially prone to underusing the cream once that structured accountability disappears. The authors argued that replicating trial-level efficacy in practice will likely require deliberate adherence support, including patient education, reminder systems, and more frequent follow-up, so that a treatment that looked as effective as an injectable biologic in clinical trials does not underperform once patients take it home.

References

1. D'Souza N, Feldman SR. Topical delgocitinib for moderate to severe atopic hand eczema: premature or promising? J Dermatolog Treat. 2026;37(1):2697408. doi:10.1080/09546634.2026.2697408
2. Quaade AS, Alinaghi F, Dietz JB, Erichsen CY, Johansen JD. Chronic hand eczema: a prevalent disease in the general population associated with reduced quality of life and poor overall health measures. Contact Dermatitis. 2023;89(6):453-463. doi:10.1111/cod.14407