Topical JAK inhibitor scores big in CHE

Treatment with the investigational, topical pan-JAK inhibitor delgocitinib cream led to significantly greater improvements in efficacy outcomes compared with the vehicle cream in moderate-to-severe chronic hand eczema (CHE) in the pivotal phase III DELTA 1 trial, offering a rational strategy for targeted therapy.

“CHE is associated with pain and pruritus and has a huge impact on quality of life,” said study author Dr Robert Bissonnette, a dermatologist and founder and CEO of Innovaderm Research, at AAD 2023. “Current topical treatments are often insufficient. Safe and efficacious treatments are therefore warranted.”

Delgocitinib works by inhibiting activation of the JAK-STAT pathway and targeting key mediators of CHE.

Building from a previous trial

In a previous 16-week randomized phase IIb dose-ranging trial, twice-daily treatment with delgocitinib cream demonstrated significantly greater efficacy vs vehicle treatment and was well tolerated. [Br J Dermatol 2022;187:42-51]

In the current DELTA 1 trial, Bissonnette and his team randomly assigned 487 adults with moderate- to-severe CHE to delgocitinib cream 20 mg/g twice-daily applications (n=325) or cream vehicle (n=162) for 16 weeks. The median age of the patients was 44 years. Eighty-eight percent were White, 4 percent were Asians, 1 percent Black, and the others were from other racial groups.

One-third of the patients had severe hand eczema based on their Investigator’s Global Assessment for chronic hand eczema (IGA-CHE) score. The median Hand Eczema Severity Index (HECSI) was 65 (severe disease), and the median Dermatology Life Quality Index (DLQI) was 12. Nineteen percent had undergone phototherapy, 14 percent had tried oral retinoids, and 12 percent had tried oral corticosteroids previously.

At the end of 16 weeks, patients had the option to enter a 36-week extension trial which is currently ongoing.

When available topical therapies fail

DELTA 1 included adult patients with CHE (hand eczema that had persisted for >3 months or had returned more than twice within the past 12 months, an IGA-CHE score of 3 or 4 (moderate or severe), a weekly average Hand Eczema Symptom Diary (HESD) itch score of ≥4 points, and a history of inadequate response to topical corticosteroids within the past 12 months, or for whom treatment with topical corticosteroids was not suitable).

The IGA-CHE scale used in the trial was new, Bissonnette explained.  “To be almost clear, the only sign that should be present on the skin was barely perceptible erythema.”

Having been involved in countless studies, he said he had used several IGA scales in the past, “but this was the first [study] that used a scale with a bar so high.”

Secondary endpoints included a 75-percent and 90-percent improvement in HECSI and a ≥4-point improvement in DLQI, both from baseline to week 16.

At week 4, there were more patients in the delgocitinib arm than the vehicle arm who achieved IGA-CHE 0/1 (15.4 percent vs 4.9 percent; p<0.001), and similarly at week 8 (22.8 percent vs. 10.5 percent; p= 0.001). Week 16 saw almost similar results with delgocitinib (19.7 percent vs. 9.9 percent; p=0.006).

In terms of the secondary endpoints, there were more patients in the delgocitinib arm who achieved a HECSI-75 (49.2 percent vs 23.5 percent), a HECSI-90 (29.5 percent vs 12.3 percent), and a ≥4-point improvement in DLQI than those in the vehicle arm (74.4 percent vs 50 percent; p<0.001 for all).

Comparable safety profile

There was no difference between arms in the proportion of patients who had adverse events as well as serious adverse events, the most common being COVID-19 infections and nasopharyngitis.

“The findings move us closer to a potential first-in-class approved therapy for CHE,” the investigators said.