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Background: Chronic hand eczema is a fluctuating, inflammatory, pruritic, often painful disease of hands and wrists that strongly impacts quality of life and occupational capabilities of patients. The aim of phase 3 DELTA 1 and DELTA 2 was to assess the efficacy and safety of twice-daily applications of the topical pan-Janus kinase inhibitor delgocitinib cream 20 mg/g versus cream vehicle in adults with moderate to severe chronic hand eczema., Methods: Both trials were randomised, double-blinded, and vehicle-controlled, with DELTA 1 being conducted at 53 trial centres in Canada, France, Germany, Italy, Poland, and the UK and DELTA 2 at 50 trial centres in Belgium, Canada, Denmark, Germany, the Netherlands, Poland, and Spain. Adults (aged ≥18 years) with moderate to severe chronic hand eczema were randomly assigned 2:1 to twice-daily delgocitinib cream 20 mg/g or cream vehicle for 16 weeks. The primary endpoint was Investigator's Global Assessment for Chronic Hand Eczema (IGA-CHE) treatment success at week 16, defined as IGA-CHE score of 0 (clear) or 1 (almost clear, defined as only barely perceptible erythema). Efficacy and safety were assessed in all patients who were exposed to trial treatment. These trials are registered with ClinicalTrials.gov, NCT04871711 and NCT04872101., Findings: Between May 10, 2021, and Oct 31, 2022, 487 patients (181 male and 306 female) were enrolled in DELTA 1; between May 25, 2021, and Jan 6, 2023, 473 patients (161 male and 312 female) were enrolled in DELTA 2. 325 patients in DELTA 1 and 314 in DELTA 2 were assigned to delgocitinib cream; 162 patients in DELTA 1 and 159 in DELTA 2 were assigned to cream vehicle. At week 16, a greater proportion of delgocitinib-treated patients versus cream vehicle patients had IGA-CHE treatment success (64 [20%] of 325 vs 16 [10%] of 162 in DELTA 1 and 91 [29%] of 313 vs 11 [7%] of 159 in DELTA 2; both trials p≤0·0055). The proportion of patients who reported adverse events was similar with delgocitinib (147 [45%] of 325 in DELTA 1 and 143 [46%] of 313 in DELTA 2) and the cream vehicle (82 [51%] of 162 in DELTA 1 and 71 [45%] of 159 in DELTA 2). Most frequent adverse events occurring in at least 2% of patients were similar in both treatment groups and included COVID-19 and nasopharyngitis., Interpretation: Overall, delgocitinib cream showed superior efficacy versus cream vehicle and was well tolerated over 16 weeks. These results support the clinical benefit of delgocitinib cream as a potential treatment option for patients with moderate to severe chronic hand eczema, who are unable to adequately control their disease with basic skin care practices and topical corticosteroids., Funding: LEO Pharma., Competing Interests: Declaration of interests RB is an advisory board member, consultant, speaker, or investigator for and receives honoraria or grants from AbbVie, Amgen, Apogee, Arcutis, Asana BioSciences, Bellus Health, BioMimetix, Bluefin Biomedicine, Boehringer Ingelheim, Boston, CARA Therapeutic, Clexio, Dermavant, Eli Lilly, Escient, Evidera, Fresh Tracks (Brickell), Galderma, GlaxoSmithKline, Incyte, Inmagene Bio, Janssen, LEO Pharma, Merck, Novartis, Opsidio, Pfizer, RAPT Therapeutic, Regeneron, Sanofi, Target RWE, Vyne Therapeutics, and Xencor. RB is also an employee and shareholder of Innovaderm Research. RBW has received research grants or consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DiCE, GSK, Janssen, Lilly, LEO Pharma, Novartis, Pfizer, Sanofi, Sun Pharma, UCB, and UNION. AP has served as an investigator, speaker, or advisor for AbbVie, Almirall-Hermal, Amgen, Biogen Idec, Biontec, Boehringer Ingelheim, BMS, Celgene, Celltrion, GSK, Eli Lilly, Galderma, Hexal, Janssen, LEO Pharma, MC2, Medac, Merck Serono, Mitsubishi, MSD, Novartis, Pascoe, Pfizer, Tigercat Pharma, Regeneron, Roche, Sandoz Biopharmaceuticals, Sanofi-Genzyme, Schering-Plough, UCB Pharma, and Zuellig Pharma. TA has given lectures, participated in clinical trials, or been on advisory boards for Sanofi, LEO Pharma, Pfizer, Eli Lilly, Galderma, and AbbVie. MG has been an investigator, speaker, or advisor for AbbVie, Acelyrin, Amgen, Akros, Arcutis, Aristea, AnaptysBio, Apogee, Bausch Health, BMS, Boehringer Ingelheim, Celgene, Dermira, Dermavant, Eli Lilly, Galderma, GSK, Incyte, InMagene, Janssen, Kyowa Kirin, LEO Pharma, MedImmune, Meiji, Merck, Moonlake, Nimbus, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, Tarsus, Takeda, UCB, Union, and Ventyx. MLAS has been a consultant, advisory board member, investigator, or speaker for Sanofi Genzyme, Regeneron Pharmaceuticals, Pfizer, LEO Pharma, Eli Lilly, Galderma, AbbVie, Novartis, and Amgen. M-NC is a consultant, advisory board member, investigator, or speaker for AbbVie, Eli Lilly, LEO Pharma, Novartis, Pfizer, and Sanofi Genzyme. LS has been principal investigator in clinical trials sponsored by or has received personal fees for participation in advisory boards from AbbVie, Amgen, LEO Pharma, Eli Lilly, Novartis, and Sanofi, outside the submitted work. ES-B has served as an investigator or speaker or advisor for AbbVie, Almirall-Hermal, Lilly, LEO Pharma, Pfizer, Sanofi, Novartis, and Galderma. KB, MK, and UP are employees of LEO Pharma. SK and NSV were employees of LEO Pharma. SS is or has been a consultant, advisory board member, investigator, or speaker for LEO Pharma, Sanofi-Aventis, Novartis Pharma, Lilly Pharma, and AbbVie. All investigators had confidentiality agreements with the sponsor., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Chronic hand eczema (CHE) is a burdensome disease, and new well-documented, safe and efficacious treatments are warranted. In a recent CHE phase IIa trial, the pan-Janus kinase (JAK) inhibitor delgocitinib in an ointment formulation was found to be efficacious and well tolerated., Objectives: This trial assessed the dose response, efficacy and safety of delgocitinib cream in CHE., Methods: In this double-blind, phase IIb dose-ranging trial, adults with CHE and a recent history of inadequate response or contraindication to topical corticosteroids were randomized to delgocitinib cream 1, 3, 8, 20 mg g -1 or vehicle treatment twice daily for 16 weeks. The primary endpoint was the Investigator's Global Assessment for CHE (IGA-CHE) treatment success [0 (clear) or 1 (almost clear) with a ≥ two-point improvement from baseline to week 16]. Secondary endpoints were the time to IGA-CHE treatment success and changes in Hand Eczema Severity Index (HECSI); other endpoints were itch and pain numerical rating scale (NRS) scores, and Patient's Global Assessment (PaGA) at week 16., Results: Patients (n = 258) were randomized 1 : 1 : 1 : 1 : 1 to delgocitinib cream 1, 3, 8, 20 mg g -1 or vehicle. A significant dose-response relationship was established for IGA-CHE (P < 0.025). IGA-CHE treatment success at week 16 was achieved in 21.2% (1 mg g -1 ), 7.8% (3 mg g -1 ), 36.5% (8 mg g -1 ), 37.7% (20 mg g -1 ) and 8.0% (vehicle) of patients. Delgocitinib 8 and 20 mg g -1 showed a treatment effect against vehicle (P < 0.001). Similarly, there were improvements in HECSI, itch and pain NRS scores, and PaGA. Delgocitinib cream was well tolerated with the majority of adverse events being mild or moderate and considered unrelated to treatment. The most frequently reported adverse events were nasopharyngitis (17.3-29.4% in delgocitinib groups vs. 40% in vehicle group), eczema (5.8-11.3% in delgocitinib groups vs. 16.0% in vehicle group) and headache (3.8-11.5% in delgocitinib groups vs. 4.0% in vehicle group)., Conclusions: In this trial, delgocitinib cream showed a dose-response relationship in terms of efficacy and was well tolerated., (© 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)