delgocitinib and Pruritus

Measuring patient-reported outcomes is crucial to fully capture the burden of chronic hand eczema (CHE).. To assess the effect of delgocitinib cream on itch, pain and nine additional key signs and symptoms reported by patients with CHE using the Hand Eczema Symptom Diary (HESD).. In a double-blind, phase IIb dose-ranging trial (NCT03683719), 258 adults with mild to severe CHE were randomized to delgocitinib cream 1, 3, 8 or 20 mg/g or cream vehicle twice daily for 16 weeks. Patients assessed 11 signs and symptoms of CHE daily through the HESD using an 11-point numeric rating scale; this was an exploratory endpoint.. Delgocitinib cream 20 mg/g was associated with an early and sustained reduction in itch and pain, along with clinically relevant reductions of ≥4 points from baseline to Week 16 in 48.4% and 63.6% of patients, respectively (17.9% and 5.9% with cream vehicle). There were improvements versus cream vehicle in all assessed CHE signs and symptoms (20 mg/g, p < 0.05).. Delgocitinib cream reduced itch, pain and other signs and symptoms in patients with CHE. This data correlated with clinician-reported outcomes, indicating that the HESD may be a useful assessment tool for CHE management.

Topics: Adult; Dermatitis, Allergic Contact; Double-Blind Method; Eczema; Emollients; Humans; Pain; Pruritus; Treatment Outcome

Chronic hand eczema (CHE) is a burdensome disease, and new well-documented, safe and efficacious treatments are warranted. In a recent CHE phase IIa trial, the pan-Janus kinase (JAK) inhibitor delgocitinib in an ointment formulation was found to be efficacious and well tolerated.. This trial assessed the dose response, efficacy and safety of delgocitinib cream in CHE.. In this double-blind, phase IIb dose-ranging trial, adults with CHE and a recent history of inadequate response or contraindication to topical corticosteroids were randomized to delgocitinib cream 1, 3, 8, 20 mg g. Patients (n = 258) were randomized 1 : 1 : 1 : 1 : 1 to delgocitinib cream 1, 3, 8, 20 mg g. In this trial, delgocitinib cream showed a dose-response relationship in terms of efficacy and was well tolerated.

Topics: Adult; Dermatitis, Atopic; Double-Blind Method; Eczema; Emollients; Humans; Immunoglobulin A; Janus Kinase Inhibitors; Pain; Pruritus; Pyrroles; Severity of Illness Index; Treatment Outcome

JTE-052 is a novel Janus kinase inhibitor presently under clinical development for the topical treatment of atopic dermatitis (AD).. To evaluate the efficacy and safety of JTE-052 ointment in Japanese adult patients with AD.. Patients with moderate-to-severe AD were randomized (2: 2: 2: 2: 1: 1) to receive JTE-052 ointment at 0·25%, 0·5%, 1% or 3%, the vehicle ointment or tacrolimus 0·1% ointment (reference) twice daily for 4 weeks. The primary efficacy end point was the percentage change in modified Eczema Area Severity Index (mEASI) score from baseline at the end of treatment (EOT). Secondary efficacy end points included change from baseline in the pruritus numerical rating scale (NRS) score.. In total, 327 patients were enrolled. At EOT, the least-squares mean percentage changes from baseline in mEASI score for JTE-052 at 0·25%, 0·5%, 1% and 3% and the vehicle ointment were -41·7%, -57·1%, -54·9%, -72·9% and -12·2%, respectively. All JTE-052 groups showed significant reductions of mEASI score vs. the vehicle group (P < 0·001 for all). In the tacrolimus group, the mean percentage change in mEASI score was -62·0%. The JTE-052 groups also showed significant improvement in other parameters; notably, the pruritus NRS score was reduced as early as day 1 night-time. JTE-052 ointment at doses up to 3% was safe and well tolerated.. Topical JTE-052 markedly and rapidly improved clinical signs and symptoms in Japanese adult patients with moderate-to-severe AD, with a favourable safety profile. The study results indicate that topical JTE-052 is a promising therapeutic option for AD. The trial registration number is JapicCTI-152887.

Topics: Administration, Cutaneous; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Dermatitis, Atopic; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Ointments; Pruritus; Pyrroles; Treatment Outcome; Young Adult

The purpose of the present two phase 1 studies was to assess the safety, tolerability and pharmacokinetics for topical application of a novel Janus kinase (JAK) inhibitor, JTE-052, in Japanese healthy adult male volunteers and Japanese adult patients with atopic dermatitis (AD). Additionally, exploratory investigation was performed on the efficacy for disease severity and pruritus score in AD patients. In the QBX1-1 study, the cutaneous safety of JTE-052 ointment by a patch test and a photo patch test was assessed in an intra-individual comparative study using placebo ointment, white petrolatum and non-application as comparators. The study demonstrated that JTE-052 ointment would be associated with a low potential for phototoxicity but had no potential for skin irritation or photoallergy. In the QBX1-2 study, it was revealed that the systemic exposure to JTE-052 in both healthy volunteers with normal skin and AD patients with inflamed skin was low in application of not only 1% but also 3% JTE-052 ointment. JTE-052 ointments of 1% and 3% were generally safe and well tolerated in both populations. In a repeated twice-daily application for 7 days, the efficacy of JTE-052 ointment to AD patients was observed with both 1% and 3% ointments in the exploratory investigations evaluated by Eczema Area and Severity Index, Investigator's Global Assessment and Numeric Rating Scale assessments. The mean scores for each assessment declined from the baseline throughout the study. These results suggest that the treatment of JTE-052 ointment is generally safe and effective in AD patients, although further large confirmatory studies are needed.

Topics: Administration, Cutaneous; Adult; Dermatitis, Atopic; Dermatitis, Phototoxic; Female; Healthy Volunteers; Humans; Janus Kinase Inhibitors; Japan; Male; Middle Aged; Ointments; Patch Tests; Placebos; Pruritus; Pyrroles; Severity of Illness Index; Skin; Treatment Outcome; Young Adult

Topics: Administration, Cutaneous; Animals; Antipruritics; Dermatitis, Atopic; Disease Models, Animal; Female; Humans; Janus Kinase Inhibitors; Male; Mice; Pruritus; Pyrroles; Skin