Novel Pan-JAK Inhibitor Cream Improves Chronic Hand Eczema Symptoms

A first-in-class topical pan-Janus kinase (JAK) inhibitor significantly improved symptoms of moderate to severe chronic hand eczema in two randomized phase III trials.

At week 16, more patients treated with delgocitinib cream had Investigator’s Global Assessment for Chronic Hand Eczema (IGA-CHE) treatment success compared with patients treated with a cream vehicle: 20% vs 10% in the DELTA 1 trial and 29% vs 7% in the DELTA 2 trial (both trials P≤0.0055), reported researchers led by Robert Bissonnette, MD, of Innovaderm Research in Montreal.

“The data from the DELTA 1 and DELTA 2 trials support the use of delgocitinib cream in adults with moderate to severe chronic hand eczema as an efficacious and well tolerated topical treatment, suggesting an innovative treatment option for relief of clinical signs and symptoms in this often difficult-to-treat patient population,” they wrote in The Lancet.

Delgocitinib blocks the signaling of JAK-dependent cytokines, thereby downregulating the inflammatory responses associated with chronic hand eczema, Bissonnette and team explained.

“The results of both trials confirm the key role of the JAK-associated signal transduction pathways in chronic hand eczema,” they noted, “supporting the use of delgocitinib due to its mode of action, and indicates that all JAKs might need to be antagonized.”

In an accompanying editorial, Yael Renert-Yuval, MD, of Schneider Children’s Medical Center of Israel in Petah Tikva, and Emma Guttman-Yassky, MD, PhD, of the Icahn School of Medicine at Mount Sinai in New York City, said the two studies are the first phase III trials to establish the potential use of a topical pan-JAK inhibitor in chronic hand eczema, addressing a “huge unmet need” in the field.

“Chronic hand eczema is also challenging to manage, as it can be difficult to identify and avoid contact irritants and allergens in many cases,” they wrote. “Given that the hands are crucial for occupational and social purposes, both skin function and appearance in this location are of immense importance to patients.”

“With a satisfactory safety and tolerability profile, a clear advantage of topical JAK inhibitors is the potential for long-term use without the common skin atrophy encountered with topical corticosteroids,” they added. “Long-term extension results are important to further support these safety findings and to establish sustained efficacy.”

DELTA 1 and DELTA 2 were double-blind, parallel-group trials in which adults with moderate to severe chronic hand eczema were treated with delgocitinib cream 20 mg/g twice daily for 16 weeks. Patients in control groups used the cream vehicle twice daily.

DELTA 1 was conducted at 53 research centers and hospitals in Canada, France, Germany, Italy, Poland, and the U.K. from May 2021 to October 2022 among 487 patients. Mean age was 44, 63% were women, and 88% were white. Mean age at onset of chronic hand eczema was 32, and mean duration of the condition was 6 years.

DELTA 2 was conducted at 50 centers and hospitals in Belgium, Canada, Denmark, Germany, the Netherlands, Poland, and Spain from May 2021 to January 2023 among 473 patients. Mean age was 44, 66% were women, and 93% were white. Mean age at onset of chronic hand eczema was 34, and mean duration of the condition was 5 years.

Both trials included up to a 4-week screening period, 16 weeks of treatment, and a 2-week safety follow-up period.

The primary endpoint for both trials was IGA-CHE treatment success at week 16, defined as a score of 0 (clear) or 1 (almost clear), with at least a two-step improvement from baseline. Secondary endpoints included improvements in the Hand Eczema Severity Index (HESCI) score and reductions in pain and itching in the patient-reported Hand Eczema Symptom Diary (HESD) from baseline to week 16, which were also significantly better in the treatment group.

Approximately 30% of delgocitinib-treated patients in DELTA 1 and 31% in DELTA 2 experienced a 90% improvement in HESCI score, compared with 12% and 9% of patients in the cream vehicle control groups (P<0.0001).

In DELTA 1, the least squares mean change in HESD pain score from baseline was -3.4 in patients treated with delgocitinib cream and -1.8 in the cream vehicle group (P<0.0001). Results for the HESD pain score were similar in DELTA 2.

The proportion of patients reporting adverse events was similar in the treatment and control groups: 45% versus 51% in DELTA 1 and 46% versus 45% in DELTA 2. The most frequent adverse events, occurring in at least 2% of patients, were similar in both treatment groups and included COVID-19 and nasopharyngitis.

No adverse events of special interest with JAK inhibitors were reported, including severe infections, cardiovascular events, or venous thromboembolism. The long-term safety of delgocitinib is being investigated in an open-label extension trial (DELTA 3) of patients who completed DELTA 1 or DELTA 2.

Bissonnette and colleagues noted that a limitation of their study was the majority-white population, in addition to the relatively short 16-week treatment period.

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