Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema (DELTA 1 and DELTA 2): results from multicentre, randomised, controlled, double-blind, phase 3 trials.

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.

Calcipotriol/Betamethasone Dipropionate Cutaneous Foam Treatment for Psoriasis in Patients With BSA 5-15% and PGA ≥ 3: Post-Hoc Analysis From Three Randomized Controlled Trials.

INTRODUCTION: Psoriasis is a chronic, inflammatory disease, which ranges in severity from mild to severe. Although topical therapies are frequently used to treat mild disease, they are not routinely used to treat patients with moderate-to-severe disease who have a larger proportion of their body surface area (BSA) affected (≥ 5% BSA). Based on well-controlled trials in adults with mild-to-severe disease, fixed-dose combination calcipotriol 50 µg/g + betamethasone dipropionate 0.5 mg/g (Cal/BD) cutaneous foam has been approved (Enstilar®, LEO Pharma) in the USA and EU for the treatment of psoriasis vulgaris for up to 4 weeks in adults. In this post-hoc subgroup analysis, we used pooled data from phase II/III trials to investigate the efficacy and safety of Cal/BD cutaneous foam in patients with moderate-to-severe psoriasis. METHODS: Patients included in this analysis had psoriasis affecting 5-15% BSA and a physician's global assessment (PGA) ≥ 3. Endpoints included: treatment success by PGA (rating: clear/almost clear), patient's global assessment (PaGA) at week 4 (rating: clear/very mild) and safety. RESULTS: A total of 340 patients in the three randomized trials met the BSA/PGA inclusion criteria, of whom 254 were treated with Cal/BD foam and 86 with vehicle foam. Treatment success by PGA and PaGA at week 4 was achieved in 143 (58.1%) and 138 (56.1%) patients receiving Cal/BD foam, respectively, versus three (3.6%) and 14 (16.7%) patients receiving vehicle foam. Sixty-six adverse events (AEs) occurred in 47 (18.5%) patients receiving Cal/BD foam and 11 AEs occurred in 11 (12.8%) patients receiving vehicle foam. Three severe AEs and 15 non-serious treatment-related AEs occurred in patients receiving Cal/BD foam. CONCLUSION: The results from three clinical trials analyzed together show that topical Cal/BD foam is well tolerated and efficacious for treating patients with moderate-to-severe disease. Data support Cal/BD foam as a potential topical therapy for moderate-to-severe psoriasis. TRIAL REGISTRATIONS: ClinicalTrials.gov registration numbers: NCT01866163, NCT02132936, NCT01536886.

Calcipotriol plus betamethasone dipropionate gel compared with calcipotriol scalp solution in the treatment of scalp psoriasis: a randomized, controlled trial investigating efficacy and safety in a Chinese population.

BACKGROUND: Calcipotriol/betamethasone dipropionate combination in a non-alcoholic, lipophilic gel formulation (two-compound gel) has previously been demonstrated as a safe and effective treatment for scalp psoriasis in Caucasian, Hispanic/Latino, and Black/African American populations. The purpose of this randomized, investigator-blinded, active-controlled, 4-week study was to evaluate the efficacy and safety of the two-compound gel in Chinese subjects with scalp psoriasis. METHOD: Subjects were randomized in a 1 : 1 ratio to four weeks of treatment with either the two-compound gel once daily or calcipotriol scalp solution twice daily. Subjects were evaluated after one, two, and four weeks of treatment. The primary efficacy endpoint was the proportion of subjects who achieved "controlled disease" defined as "clear" or "minimal" disease according to investigator's global assessment of disease severity at week 4. RESULTS: The proportion of subjects who achieved "controlled disease" at week 4 was statistically significantly higher in the two-compound gel group (87.5%) than in the calcipotriol solution group (50.8%), (P < 0.0001). Greater and more rapid improvements with the two-compound gel were also observed in clinical signs (redness, thickness, and scaliness) and itching. The two-compound gel was associated with fewer adverse drug reactions than calcipotriol scalp solution (18.6% vs. 33.1%) (P = 0.011). CONCLUSIONS: The calcipotriol/betamethasone dipropionate gel applied once daily was significantly more effective and better tolerated than calcipotriol scalp solution applied twice daily in the treatment of scalp psoriasis over four weeks in Chinese subjects.

Safety and efficacy of calcipotriene plus betamethasone dipropionate topical suspension in the treatment of extensive scalp psoriasis in adolescents ages 12 to 17 years.

The objective of this study was to assess the safety and efficacy of the fixed combination calcipotriene 0.005% plus betamethasone dipropionate 0.064% topical suspension in adolescents with extensive scalp psoriasis. In this phase II, open-label, 8-week study, adolescents with psoriasis (ages 12-17 years) with 20% or more of the scalp area affected (at least moderate severity according to Investigator's Global Assessment [IGA]) were assigned to once-daily treatment with calcipotriene plus betamethasone dipropionate topical suspension. The primary endpoint was safety, focusing on calcium metabolism and hypothalamic-pituitary-adrenal axis function. Secondary efficacy endpoints were the proportion of patient's achieving treatment success (clear or almost clear disease according to the IGA and clear or very mild disease according to the Patient's Global Assessment [PaGA]) and percentage change in investigator-assessed Total Sign Score (TSS). Pruritus was also assessed. Overall, 31 patients received treatment. Sixteen patients (52%) experienced a total of 20 adverse events; 19 were considered unrelated to study treatment, 14 were mild, and none were serious or lesional or perilesional on the scalp. One patient showed signs of mild adrenal suppression at week 4; the patient discontinued treatment and had normal test results at follow-up 4 weeks later. No cases of hypercalcemia were reported. By treatment end, treatment success was reported for 17 patients (55%) according to the IGA and 18 (58%) according to the PGA. Mean TSS improved from 6.9 at baseline to 2.9 at treatment end (59% improvement). By week 8, 28 patients (90%) experienced mild or no itching, versus 20 (65%) at baseline. Once-daily calcipotriene plus betamethasone dipropionate topical suspension was well tolerated and efficacious for the treatment of scalp psoriasis in adolescents.