The purpose of this study is to investigate the efficacy of dupilumab in hand eczema patients with an inadequate response or intolerance to alitretinoin.

Inclusion Criteria:

• Age ≥ 18 years and ≤ 75 years.
• Severe or very severe chronic hand eczema as defined by a Physician Global Assessment (PGA) using a validated Photoguide.
• Inflammatory subtypes of hand eczema: recurrent vesicular hand eczema or chronic fissured hand eczema.
• An inadequate response to topical corticosteroids within 6 months before screening.
• A history of prior alitretinoin exposure and inadequate response or intolerance to alitretinoin.
• Patients has also received standard skin care, including emollients and barrier protection as appropriate, without significant improvement.
• Patients has avoided irritants and contact allergens, if identified, without significant improvement.
• Women of childbearing potential are required to use a highly effective (failure rate of <1% per year when used consistently and correctly) method of birth control, prior to receiving study intervention, during the study and for at least 10 weeks after receiving the last administration of study intervention. E.g., established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; barrier methods: condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal foam/gel/film/cream/suppository (if available in their locale); male partner sterilization (the vasectomized partner should be the sole partner for that participant); true abstinence (when this is in line with the preferred and usual lifestyle of the participant). NOTE: If a female participant's childbearing potential changes after start of the study (e.g., a woman who is not heterosexually active becomes active, a premenarchal woman experiences menarche), she must begin practicing a highly effective method of birth control, as described above.
• A woman of childbearing potential must have a negative serum or urine pregnancy test (β-human chorionic gonadotropin [β-hCG]) at screening and at Week 0 prior to administration of study intervention;
• Agree not to receive a live virus or live bacterial vaccination during the study, or within 12 weeks after the last administration of study intervention.
• Agree not to receive a Bacillus Calmette-Guérin (BCG) vaccination during the study, or within 12 months after the last administration of study intervention.
• Be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
• Must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study, and is willing to participate in the study.

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

• Other clinical subtypes of hand eczema, e.g. hyperkeratotic hand eczema, as defined by the Danish Contact Dermatitis Group24.
• Treatment with alitretinoin, systemic immunosuppressive medication or UV radiation within the previous 4 weeks.
• Patients with predominantly atopic dermatitis, in whom the hands are also involved, but no main concern. Patients with controlled atopic dermatitis, in which the hands are mainly affected, are eligible for inclusion.
• Psoriasis of the hands.
• Active bacterial, fungal, or viral infection of the hands.
• Pregnant/lactating or planning to become pregnant during the study period.
• Current malignancy (other than successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and⁄or localized carcinoma in situ of the cervix).
• Participant has known allergies, hypersensitivity, or intolerance to dupilumab or its excipients: L-arginine hydrochloride, L-histidine, polysorbate 80, sodium acetate, acetic acid, sucrose, water for injections.
• Participants with active helminth and other parasitic infections.
• Patients infected with human immunodeficiency virus (HIV) (positive serology for HIV antibody).
• Patients testing positive for hepatitis B virus (HBV) or hepatitis C (HCV) infection.

Data will be published anonymously and will not be possible to trace back to individual participants.