Delgocitinib

Delgocitinib is a Janus kinase inhibitor (pan-Janus kinase (JAK) inhibitor) that blocks the signaling of proinflammatory cytokines by inhibiting the JAK-STAT pathway. It is used for the topical treatment of moderate to severe chronic hand eczema in adults (Worm M et al. 2022) where glucocorticoids are insufficient or unsuitable. Delgocitinib has been approved in the EU as a cream with a concentration of 20 mg delgocitinib per gram of cream (2%) since September 2024.

Delgocitinib is a pan-Janus kinase (JAK) inhibitor that inhibits the activity of all four members of the JAK enzyme family - JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2) - in a concentration-dependent manner. These enzymes are essential for signal transduction in the JAK-STAT signaling pathway, which plays a central role in the regulation of immune responses and inflammatory processes.

In human cells, delgocitinib blocks the activation and transmission of pro-inflammatory cytokines such as interleukin (IL)-2, IL-4, IL-6, IL-13, IL-21 and IL-23 as well as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon (IFN)-alpha by inhibiting this signaling pathway. These cytokines are significantly involved in the development and maintenance of inflammatory reactions that cause the symptoms of chronic hand eczema.

By inhibiting the JAK-STAT pathway, the signaling of these cytokines is attenuated, leading to a reduction in a hyperactive immune response. This results in a downregulation of inflammatory reactions in the affected skin cells. The result is an anti-inflammatory effect. In particular, there is a reduction in erythema, scaling and itching, characteristics of chronic hand eczema.

Delgocitinib is a pan-Janus kinase inhibitor indicated for the treatment of moderate to severe chronic hand eczema (CHE) in adults in whom topical corticosteroids are inadequate or unsuitable.

In the DELTA FORCE head-to-head study, delgocitinib cream was shown to be superior to alitretinoin in patients with severe CHE (Giménez-Arnau AM et al. 2025).

Good clinical effects can also be achieved in atopic dermatitis (Ho J et al. 2021). Different clinical results are achieved in alopecia areata (Mikhaylov D et al. 2023; Liu M et al. 2023).

Delgocitinib is a pan-Janus kinase inhibitor indicated for the treatment of moderate to severe chronic hand eczema (CHE) in adults where topical corticosteroids are inadequate or unsuitable. Good clinical effects can also be achieved in atopic dermatitis (Ho J et al. 2021). Different clinical results are achieved in alopecia areata (Mikhaylov D et al. 2023; Liu M et al. 2023).

The product should be applied thinly twice daily to clean and dry skin. The safety and efficacy in children under 18 years of age has not yet been investigated.

The most common side effects in the first week of treatment are local irritation at the application sites (redness, itching, pain). These subside after three days on average.

Studies on interactions with topically or systemically applied delgocitinib have not been conducted. Due to the minimal systemic exposure of delgocitinib, the risk of interactions with systemic therapies is low. The concomitant use of delgocitinib with other topical products on the same skin sites is not recommended.

Delgocitinib is also systemically effective to a small extent after topical application. Approximately 22-29% of the systemically available portion after topical application is bound to plasma proteins. However, only unbound portions of the JAK inhibitors are effective.

Delgocitinib must not be used in case of hypersensitivity to delgocitinib or any of the other ingredients.

^Anzupgo® 20 mg/g cream/LEO Pharma GmbH.

The following warnings and precautions should be observed when using delgocitinib:

Nonmelanocytic skin cancer: The occurrence of nonmelanocytic skin cancer, particularly basal cell carcinoma, has been reported in patients treated with topical JAK inhibitors. Regular skin examinations of the application sites are recommended, especially in patients with known risk factors for skin cancer.

Benzyl alcohol: This medicinal product contains benzyl alcohol which may cause allergic reactions or mild local irritation.

Butylated hydroxyanisole: The ingredient butylated hydroxyanisole may cause local skin irritation (e.g. contact dermatitis) and irritation of the eyes and mucous membranes.

Cetylstearyl alcohol: Cetylstearyl alcohol may cause localized skin irritation such as contact dermatitis.

1. Bissonnette R et al. (2024) Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema (DELTA 1 and DELTA 2): results from multicentre, randomized, controlled, double-blind, phase 3 trials. Lancet 404:461-473.
2. Giménez-Arnau AM et al. (2025) Efficacy and safety of topical delgocitinib cream versus oral alitretinoin capsules in adults with severe chronic hand eczema (DELTA FORCE): a 24-week, randomized, head-to-head, phase 3 trial. Lancet 405:1676-1688.
3. Ho J et al. (2021) Delgocitinib in atopic dermatitis. Drugs Today (Barc) 57:719-731.
4. Liu M et al. (2023) Janus Kinase Inhibitors for Alopecia Areata: A Systematic Review and Meta-Analysis. JAMA Netw Open 6:e2320351.
5. Mikhaylov D et al. (2023) A phase 2a randomized vehicle-controlled multi-center study of the safety and efficacy of delgocitinib in subjects with moderate-to-severe alopecia areata. Arch Dermatol Res 315:181-189.
6. Worm M et al. (2022) The pan-JAK inhibitor delgocitinib in a cream formulation demonstrates dose response in chronic hand eczema in a 16-week randomized phase IIb trial. Br J Dermatol 187:42-51.
7. Yan T et al. (2024) Comparative efficacy and safety of JAK inhibitors in the treatment of moderate-to-severe alopecia areata: a systematic review and network meta-analysis. Front Pharmacol 15:1372810.