Delgocitinib cream shows a dose-dependent response in easing chronic hand eczema, a common and difficult-to-treat disorder for which few other topical options are available, new international phase 2b research suggests.
An investigational pan-janus kinase (JAK) inhibitor that blocks all four members of the JAK family, twice-daily delgocitinib doses of 8 mg/g and 20 mg/g demonstrated the highest efficacy in adults with mild-to-severe chronic hand eczema. By week 16, nearly 40% of patients receiving either dose were clear or almost clear of symptoms.
“By mode of action, we think delgocitinib is more selective in the way of acting,” said lead investigator Margitta Worm, MD, PhD, of Charité University Hospital in Berlin, Germany, during a presentation of the results at the 29th European Academy of Dermatology and Venereology (EADV) Congress, which was held virtually this year because of the pandemic.
“We do know that JAKs play an important role in chronic inflammation and interfering with the JAK pathway can have anti-inflammatory effects,” Worm told Medscape Medical News. “Whenever it’s possible to use a molecule topically or locally, it’s advantageous for patients because it’s only acting where you apply it and there are no systemic side effects.”
Defined as lasting more than 3 months or relapsing twice or more within a year, chronic hand eczema is a particularly problematic form of atopic dermatitis because “we need our hands every day for almost every activity, so having eczema on your hands has a huge impact on quality of life,” Worm said.
Many people whose hands are integral to their occupations also have trouble working because of the disorder, she explained. But current topical treatments are limited to emollients, corticosteroids, and calcineurin inhibitors, Worm noted.
“Topical corticosteroids are efficacious, but can cause skin atrophy,” she said. “Their long-term side-effect profile limits their use.”
The number of patients in each treatment group was too small to focus on different subtypes of chronic hand eczema, “but this is something that will probably be looked at in the future,” Worm said. “At the moment it’s nice to see a dose-dependent clinical efficacy and good tolerability, and now we have to wait for phase 3 data in the future.”
Worm and her colleagues aimed to establish the dose-response relationship of twice-daily applications of delgocitinib cream in doses of 1, 3, 8, and 20 mg/g and a delgocitinib cream vehicle for 16 weeks. The 258 participants (61% women, average age 46) were randomly assigned in equal groups to each dose of delgocitinib cream or the vehicle cream twice daily at centers in Denmark, Germany, and the United States.
The primary endpoint for the double-blind, 26-center trial was the proportion of patients who achieved an Investigator’s Global Assessment (IGA)-CHE score of 0 (‘clear’) or 1 (‘almost clear’), with a 2-point or higher improvement from baseline over the study period. A key secondary endpoint was a change in the Hand Eczema Severity Index (HECSI) from baseline to week 16.
At week 16, a statistically significant dose response was established for both primary and secondary endpoints (P < .025). More patients in the delgocitinib 8 mg/g and 20 mg/g groups met the primary endpoint (36.5% and 37.7%, respectively) than patients in the 1 mg/g and 3 mg/g groups (21.2% and 7.8%, respectively) and vehicle group (8%, P = .0004).
This primary skin clearance effect at week 16 was demonstrated from week 4 in the 8 mg/g group and week 6 in the 20 mg/g group. But all active doses achieved a statistically significant greater jump in HECSI from baseline to week 16 than the vehicle cream (P < .05).
“The strength of the trial is that there were different concentrations of the substance used,” Worm said. “When you look to the results, you can demonstrate a dose-dependent clinical efficacy. This is of great value to really compare the efficacy of single doses.”
Most adverse events reported were not considered treatment-related and were mild or moderate. The most frequently reported side effects were nasopharyngitis, eczema, and headache.
Commenting on the results, Asli Bilgic, MD, from Akdeniz University in Antalya, Turkey, who was not involved with the study, told Medscape Medical News that phase 3 studies on delgocitinib should probe further into the effects of the 8 mg/g dosage in this patient group since it appears to show similar efficacy and safety to 20 mg/g.
It’s important for research to focus on hand eczema “because it’s a very common disease, and treatment options are really sparse,” Bilgic said.
“Especially in the COVID era, many healthcare professionals, along with cleaning, catering, and mechanical jobs” are essential workers affected by the condition, she said. “It affects people’s self-esteem and their ability to do their job.”
The study was funded by LEO Pharma. Worm has received lecture honoraria from LEO Pharma. Bilgic has disclosed no relevant financial relationships.
29th European Academy of Dermatology and Venereology (EADV) Congress: Abstract 3094. Presented October 29, 2020.
Maureen Salamon is a freelance health journalist based in London and New Jersey.