Margitta Worm, MD, on a Topical Pan-JAK Inhibitor for Chronic Hand Eczema

Data from a phase 2b clinical trial¹ showed promise for a new topical pan-Janus kinase (JAK) inhibitor for the treatment of chronic hand eczema. The findings were presented at the virtual European Academy of Dermatology and Venerology Congress.

The randomized, double-blind, vehicle-controlled, parallel group study included 258 participants with atopic dermatitis who were randomized 1:1:1:1:1 to delgocitinib 1-, 3-, 8-, or 20-mg cream or vehicle twice daily for 16 weeks. Primary and second endpoints included the proportion of participants who achieved an Investigator Global Assessment for Chronic Hand Eczema score of 0 (clear) or 1 (almost clear) with an improvement of 2 or greater from baseline at week 16 and changes in the Hand Eczema Severity Index (HESCI) from baseline to week 16.

Overall, the researchers found more participants in the 8- and 20-mg groups had achieved the primary endpoint compared with those in the vehicle group (36.5% vs 37.5% vs 8%, respectively). While all delgocitinib groups showed statistically significant improvements in HESCI scores from baseline to week 16 compared with the vehicle group, earlier improvements were observed in the 8- and 20-mg groups. These statistically significant improvements were seen by week 4 in the 8-mg group and week 6 in the 20-mg group.

Furthermore, the researchers did not observe any dose-related adverse effects, and the majority of adverse effects were mild or moderate in severity. The most commonly reported adverse effects were nasopharyngitis, eczema, and headache.

In an interview with Autoimmune Learning Network, corresponding author Margitta Worm, MD, professor of dermatology with the Division of Allergy and Immunology at Charité-Universitätsmedizin in Berlin, Germany, discussed these findings.

AUTOIMMUNE LEARNING NETWORK: Could you briefly discuss the mechanisms of action for delgocitinib?

Margitta Worm: In chronic hand eczema, there is an ongoing chronic inflammatory process, and this chronic inflammation is triggered by mediators called cytokines. Cytokine production is controlled via JAKs.

Delgocitinib is a pan-JAK inhibitor, meaning that it interferes with the production of those cytokines, so there is less production and therefore less inflammation. In addition, delgocitinib has a broader anti-inflammatory approach because it is a pan-JAK inhibitor.

ALN: Could you elaborate on the significance of your findings regarding the dosing and timing of improvement?

MW: The purpose of the clinical study was to identify the optimal dose in terms of efficacy and safety. This is why these different concentrations were used in the clinical trial. A dose-dependency was observed and shown for the 8-mg and 20-mg groups. The trial was designed for a 16-week treatment phase.

The time point at which one can observe clinical effects is also of major clinical relevance. The first significant clinical effects were determined after a 4-week treatment period, meaning a relatively rapid response was seen among the proportion of patients showing an improved status of their hand eczema.

ALN: What safety signals were observed during this particular study?  

MW: In this particular trial, there were adverse events; however, there were no major differences between the vehicle group and the delgocitinib 1-, 3-, 8-, and 10-mg groups. This indicates that there is no increased risk of adverse events in principle. Second, the serious adverse events were not related to treatment.

In principle, the adverse event profile or spectrum was consistent with previous clinical trials. Headache is a common adverse event in clinical trials, as well as nasopharyngitis, and, not surprisingly, eczema itself. This is often related to the vehicle group and also if there is not sufficient clinical efficacy from the study treatment.

Each group had roughly 50 patients, so we need larger clinical trials to confirm this safety profile.

ALN: What are the next steps for this therapy?

MW: Based on the results of the phase 2b study, we can say there was clinical efficacy, and this now needs to be confirmed in a larger clinical trial. We also need data to confirm the safety profile. So far, the data look promising. 

ALN: What other takeaways would you like to leave with our audience?

MW: In general, hand eczema is very important, not only for patients in regular life, but also in occupational dermatology. There is a high medical need to have enough therapeutic possibilities for our patients.

The topical corticosteroids, which are currently the first-choice treatment, have adverse effects such as skin atrophy and proliferation of cells. Skin atrophy, particularly in hand eczema, can make the skin even more vulnerable in the long term. That is why we need more molecules with a mode of action that is unlikely to affect the skin barrier.

Reference:

1. Worm M, Thyssen J, Schliemann S, et al. The topical pan-JAK inhibitor delgocitinib cream demonstrates dose response in a 16-week phase 2b trial in chronic hand eczema. Presented at: European Academy of Dermatology and Venerology Congress; October 29, 2020; virtual.