TY - JOUR
T1 - Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema (DELTA 1 and DELTA 2)
T2 - results from multicentre, randomised, controlled, double-blind, phase 3 trials
AU - trial investigators
AU - Bissonnette, Robert
AU - Warren, Richard B.
AU - Pinter, Andreas
AU - Agner, Tove
AU - Gooderham, Melinda
AU - Schuttelaar, Marie L.A.
AU - Crépy, Marie Noëlle
AU - Stingeni, Luca
AU - Serra-Baldrich, Esther
AU - Baranowski, Keith
AU - Korn, Sofie
AU - Kurvits, Merle
AU - Plohberger, Ursula
AU - Strange Vest, Natacha
AU - Schliemann, Sibylle
AU - Lynde, Charles
AU - Guenther, Lyn
AU - Sauder, Maxwell
AU - Rao, Jaggi
AU - Day, Isaiah
AU - Devani, Alim
AU - Metelitsa, Andrei
AU - Grewal, Parbeer
AU - Molin, Sonja
AU - Ruer-Mulard, Mireille
AU - Giordano-Labadie, Françoise
AU - Maillard, Hervé
AU - Reguiai, Ziad
AU - Bernier, Claire
AU - Leleu, Camille
AU - Seneschal, Julien
AU - Staumont-Sallé, Delphine
AU - Hubiche, Thomas
AU - Jacobzone, Caroline
AU - Khemis, Abdallah
AU - Worm, Margitta
AU - Bauer, Andrea
AU - Sell, Sabine
AU - Ekanayake-Bohlig, Swarna
AU - Pauser, Sylvia
AU - Buhl, Timo
AU - Schwinn, Andreas
AU - Eberlein, Bernadette
AU - Quist, Sven
AU - Bauer, Boris
AU - Peris, Ketty
AU - Rossi, Maria Teresa
AU - Fargnoli, Maria
AU - Naldi, Luigi
AU - Ferrucci, Silvia
N1 - Publisher Copyright:
© 2024 Elsevier Ltd
PY - 2024/8/3
Y1 - 2024/8/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85199867599&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(24)01027-4
DO - 10.1016/S0140-6736(24)01027-4
M3 - Article
C2 - 39033766
AN - SCOPUS:85199867599
SN - 0140-6736
VL - 404
SP - 461
EP - 473
JO - The Lancet
JF - The Lancet
IS - 10451
ER -