THE DISORDER — Hand eczema is a common highly pruritic, inflammatory skin disorder. In addition to itching, patients may experience pain, erythema, edema, scaling, vesicles, hyperkeratosis, fissures, and lichenification. Hand eczema is more prevalent in women than in men. Risk factors include a history of atopic dermatitis, contact allergies, and exposure to "wet work" (e.g., healthcare workers, food handlers, hairdressers). The disease is considered chronic if it persists for longer than 3 months or if there are ≥2 relapses per year.2,3

STANDARD TREATMENT — Preventive measures include avoidance of irritants and use of protective gloves. Emollients and moisturizers are recommended for all patients.

Topical corticosteroids are generally used first; high-potency topical corticosteroids may be needed to achieve disease control, but serious adverse effects, such as skin atrophy, can occur with long-term use. The topical calcineurin inhibitor tacrolimus (Protopic, and generics), which is approved for treatment of atopic dermatitis, has been used for treatment of chronic hand eczema when the response to topical corticosteroids is inadequate or to minimize corticosteroid use. Tacrolimus does not cause skin atrophy. The label of tacrolimus contains a boxed warning about rare cases of lymphoma and other cancers associated with prolonged treatment, but a causal relationship has not been established.

In patients with moderate to severe disease who have had an inadequate response to topical treatments, systemic options include an oral corticosteroid (short term), cyclosporine, azathioprine, methotrexate, and acitretin, but data on their efficacy are limited and they can cause troublesome adverse effects. In one small trial, the subcutaneous interleukin (IL)-4 receptor alpha antagonist dupilumab (Dupixent) was effective for treatment of atopic hand and/or foot dermatitis that was inadequately controlled with topical corticosteroids.4 Phototherapy can be used in patients with refractory disease, but long-term use may increase the risk of skin cancer.2,3

MECHANISM OF ACTION — Delgocitinib inhibits the JAK-signal transducer and activator of transcription (STAT) pathways by blocking JAK 1, 2, and 3, and tyrosine kinase 2 (TYK2), reducing cytokine activity and inflammatory responses involved in the pathogenesis of hand eczema.

CLINICAL STUDIES — FDA approval of delgocitinib was based on the results of two double-blind trials (DELTA 1 and DELTA 2) in a total of 960 adults with moderate to severe chronic hand eczema who had an inadequate response to or could not use topical corticosteroids. Patients were randomized to apply delgocitinib cream or its vehicle alone twice daily for 16 weeks. In both trials, significantly more patients achieved clinical success (skin that was clear or almost clear with only barely perceptible erythema), the primary endpoint, with delgocitinib than with its vehicle alone (see Table 2). Delgocitinib also reduced pain and itching more than its vehicle alone.5 In an open-label extension trial (DELTA 3), response rates were maintained in patients who continued delgocitinib as needed for an additional 36 weeks.6

In an assessor-masked trial (DELTA FORCE), 513 patients with severe chronic hand eczema were randomized to receive treatment with delgocitinib cream or the oral retinoid alitretinoin (not available in the US). Delgocitinib was statistically significantly more effective than alitretinoin in reducing scores on the Hand Eczema Severity Index (HECSI; scores range from 0 to 360, with lower scores indicating less severe disease) from baseline to week 12 (least-squares mean change was -67.6 with delgocitinib vs -51.5 with alitretinoin).7

ADVERSE EFFECTS — Adverse effects of delgocitinib in clinical trials for hand eczema (reported in ≤1% of patients) included application-site pain, paresthesia, pruritus, and erythema, and leukopenia, neutropenia, and bacterial skin infections, such as finger cellulitis and paronychia.

Delgocitinib may increase the risk of serious infections. Eczema herpeticum and herpes zoster have been reported. Nonmelanoma skin cancers can occur with use of the drug; skin examinations should be performed periodically. Oral and topical JAK inhibitors have been associated with increases in lipid levels.

The label of delgocitinib cream warns about increased risks of severe adverse effects, including major adverse cardiovascular events, thrombosis, lymphoma and other malignancies, serious infections, and death, that have been observed with use of other JAK inhibitors. The warning is based on the results of a post-marketing safety trial with oral tofacitinib (Xeljanz, and others) in patients with rheumatoid arthritis and is included in the labels of other JAK inhibitors based on the presumption of a class effect.8

DRUG INTERACTIONS — Delgocitinib should not be used with other JAK inhibitors or potent immunosuppressants. Administration of live vaccines should be avoided immediately before, during, and immediately after treatment with delgocitinib.

PREGNANCY AND LACTATION — No adequate data are available on topical delgocitinib use in pregnant or lactating women. In animal studies, administration of high doses of oral delgocitinib was associated with adverse embryofetal effects.

Delgocitinib is present in the milk of lactating rats following oral administration. No data are available on the presence of the drug in human milk or its effects on the breastfed infant or milk production. After application of the cream to the hands and/or wrists, direct contact with the nipple and surrounding area should be avoided to minimize potential infant exposure.

DOSAGE, ADMINISTRATION, AND COST — Anzupgo is available in 30-gram tubes containing delgocitinib 2% cream. A thin layer should be applied to the affected areas on the hands and wrists twice daily. All age-appropriate vaccinations, including herpes zoster vaccinations, should be completed before starting delgocitinib. The wholesale acquisition cost (WAC) for a 30-gram tube of Anzupgo is about $2000.9 A 30-gram tube of generic tacrolimus ointment costs about $84.9

CONCLUSION — In two 16-week clinical trials, Anzupgo, a 2% cream formulation of the Janus kinase (JAK) inhibitor delgocitinib, was more effective than its vehicle alone for treatment of moderate to severe chronic hand eczema in patients who had an inadequate response to or were unable to use topical corticosteroids. How this expensive new product compares to use of topical tacrolimus is unknown.

REFERENCES