Delgocitinib Cream for Chronic Hand Eczema Shows Low Systemic Exposure

Even when applied at the highest amounts studied, the topical pan–Janus kinase (JAK) inhibitor delgocitinib cream (Anzupgo; LEO Pharma) produced only minimal systemic drug exposure in adults with moderate to severe chronic hand eczema (CHE), including those using the drug under maximal-use conditions, according to a brief report published in Dermatology and Therapy.¹

CHE is hand eczema that lasts for longer than 3 months or recurs at least twice within 1 year. Delgocitinib is the only FDA-approved medication specifically for CHE, although topical corticosteroids are typically used in the short term as a first-line treatment option.² Certain JAK inhibitors treating chronic inflammatory conditions were issued a boxed warning label by the FDA in 2021.³

“Systemic exposure and safety are central considerations when evaluating topical therapies for dermatological diseases,” the authors noted. “Delgocitinib cream, which was approved by the FDA without this Boxed Warning label, was formulated with minimal penetration-enhancing excipients, and without the addition of propylene glycol (PG) and polyethylene glycol (PEG), to limit systemic exposure.”

What the DELTA 2 Pharmacokinetic Data Revealed

The analysis drew on blood sampling data from the DELTA 2 phase 3 randomized, double-blind, vehicle-controlled trial, which evaluated twice-daily application of delgocitinib cream 20 mg/g in adults with moderate to severe CHE over 16 weeks. Researchers examined plasma drug concentrations among patients using the cream under normal conditions as well as a subgroup treated under maximal-use conditions, which was defined as those in the upper quartile of drug application, at 10.9 g per week or more, among patients with severe CHE.

Under normal-use conditions (n = 294), patients applied an average of 7.3 g per week across a mean body surface area (BSA) involvement of 1.48%, yielding a geometric mean plasma concentration of 0.19 ng/mL at week 1. Among the 19 patients in the maximal-use group, who applied an average of 13.7 g per week across 2.17% BSA, geometric mean plasma concentrations reached 0.58 ng/mL at week 1. Concentrations in both groups remained stable at week 4 and declined by week 16, suggesting no accumulation over time.

The researchers compared these levels against the lowest tested oral delgocitinib dose (1.5 mg) in healthy adults, which produced a peak plasma concentration of 7.2 ng/mL or roughly 12 times higher than what was observed in the maximal-use CHE group.

Low Absorption Held Even With Far Greater Body Surface Area Coverage

There was also a post hoc comparison against a phase 1 atopic dermatitis (AD) trial in which adults with moderate to severe AD and mean BSA involvement of 33.6%, or roughly 22 times the mean BSA of CHE patients in DELTA 2, applied an average of 72.3 g of delgocitinib cream per week during week 1. Despite using nearly 10 times more cream than the maximal-use CHE group, these patients showed a peak plasma concentration (geometric mean C_max) of 1.28 ng/mL on day 1 and 1.20 ng/mL on day 8, which were still well below both the lowest oral dose comparator and the in vitro pharmacological threshold.

Limitations and Longer-Term Data

The authors acknowledged several limitations. The maximal-use subgroup comprised only 19 patients, limiting the precision of those estimates. Additionally, differences in blood sampling methodology between the 2 trials—DELTA 2 used a single time point 2 to 6 hours post application, whereas the phase 1 AD trial used 6 time points over 12 hours—meant the cross-trial comparison was between geometric mean concentrations and peak C_max values, which are not directly equivalent metrics.

Longer-term safety data from the open-label DELTA 3 extension trial, which followed patients for up to 52 weeks, found twice-daily delgocitinib cream to be well tolerated with no major safety signals, adding to confidence in the drug's systemic safety profile over time.

“Low systemic exposure was observed in adults with moderate to severe AD, despite substantially greater BSA involvement and higher delgocitinib cream usage, highlighting the novel formulation of delgocitinib cream,” the authors concluded.

References

1. Gooderham M, Bunick CG, Yu J, et al. Minimal systemic exposure with maximal delgocitinib cream use in patients with severe chronic hand eczema in the DELTA 2 randomized, vehicle-controlled, double-blind, phase 3 trial. Dermatol Ther (Heidelb). Published online May 17, 2026. doi:10.1007/s13555-026-01767-1
2. Shaw ML. FDA approves delgocitinib for moderate to severe hand eczema. AJMC^®. July 24, 2025. Accessed May 29, 2026. https://www.ajmc.com/view/fda-approves-delgocitinib-for-moderate-to-severe-hand-eczema
3. Inserro A. Some JAK inhibitors to carry more black box warnings for cardiovascular concerns. AJMC. September 3, 2021. Accessed May 29, 2026. https://www.ajmc.com/view/some-jak-inhibitors-to-carry-more-black-box-warnings-for-cardiovascular-concerns