delgocitinib and Dermatitis--Allergic-Contact

Measuring patient-reported outcomes is crucial to fully capture the burden of chronic hand eczema (CHE).. To assess the effect of delgocitinib cream on itch, pain and nine additional key signs and symptoms reported by patients with CHE using the Hand Eczema Symptom Diary (HESD).. In a double-blind, phase IIb dose-ranging trial (NCT03683719), 258 adults with mild to severe CHE were randomized to delgocitinib cream 1, 3, 8 or 20 mg/g or cream vehicle twice daily for 16 weeks. Patients assessed 11 signs and symptoms of CHE daily through the HESD using an 11-point numeric rating scale; this was an exploratory endpoint.. Delgocitinib cream 20 mg/g was associated with an early and sustained reduction in itch and pain, along with clinically relevant reductions of ≥4 points from baseline to Week 16 in 48.4% and 63.6% of patients, respectively (17.9% and 5.9% with cream vehicle). There were improvements versus cream vehicle in all assessed CHE signs and symptoms (20 mg/g, p < 0.05).. Delgocitinib cream reduced itch, pain and other signs and symptoms in patients with CHE. This data correlated with clinician-reported outcomes, indicating that the HESD may be a useful assessment tool for CHE management.

Topics: Adult; Dermatitis, Allergic Contact; Double-Blind Method; Eczema; Emollients; Humans; Pain; Pruritus; Treatment Outcome

Using JAK inhibitors to inhibit cytokine signaling is presumed to be a possible means of treating skin inflammatory disorders such as contact dermatitis.. To clarify the action site of JAK inhibitors in skin inflammatory disorders.. We analyzed the mechanism of action of the JAK inhibitor JTE-052 using murine skin inflammation models, including contact hypersensitivity (CHS) and irritant contact dermatitis. Cells isolated from ear tissue or lymph node (LN) were analyzed by flow cytometry. The amounts of cytokines in the culture medium were measured by ELISA or bead array system. Proliferation of LN cells was evaluated by measurement of tritiated thymidine incorporation.. Oral administration of JTE-052 during both sensitization and elicitation phase attenuated CHS, but did not affect croton oil-induced irritant contact dermatitis. JTE-052 potently inhibited T cell proliferation and activation by antigen presentation in vitro, and attenuated skin inflammation in a sensitized-lymphocyte transfer model without suppressing T cell migration. JTE-052 did not affect hapten-induced cutaneous dendritic cell migration into draining lymph nodes or their costimulatory molecule expressions.. The JAK inhibitor JTE-052 exerts an inhibitory effect on antigen-specific T cell activation and subsequent inflammation in acquired skin immunity, such as CHS.

Topics: Administration, Oral; Animals; Antigen Presentation; Cell Differentiation; Cell Movement; Cell Proliferation; Croton Oil; Dendritic Cells; Dermatitis, Allergic Contact; Drug Evaluation, Preclinical; Female; Haptens; Inflammation; Interferon-gamma; Interleukin-13; Interleukin-17; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Protein Kinase Inhibitors; Pyrroles; Skin; T-Lymphocytes