麻豆果冻传媒影音

More than half of patients with steroid-refractory hand eczema responded quickly to a pan-Janus kinase (JAK) inhibitor in a randomized, placebo-controlled trial.

After 16 weeks of treatment, patients treated with the higher of two doses of gusacitinib had a 69.5% reduction in target lesion symptom score (TLSS), as compared with 49% among patients randomized to the lower dose of the drug, and 33.5% of placebo-treated patients. Response to gusacitinib occurred as early as 2 weeks after the start of treatment.

The higher dose of the JAK inhibitor led to a 72% improvement in the Hand Eczema Severity Index (HECSI) at 16 weeks, as compared with 20.8% in the placebo arm, reported Howard Sofen, MD, of Dermatology Research Associates and the University of California Los Angeles, at the American Academy of Dermatology virtual meeting.

"What's interesting here is that we can see efficacy as early as week 2," said Sofen. "The 80-mg group showed statistical efficacy at each time point, also with good separation from the 40-mg group and the placebo group... . When we looked at the HECSI score, another measure of hand eczema, again the 80-mg group showed good rising improvement, all the way through week 16 with statistical improvement as week 2. The 40-mg group didn't do as well, but showed superiority to placebo."

In contrast to atopic dermatitis and other inflammatory skin diseases, chronic hand eczema results in skin cracking, fissuring, and considerable pain, Sofen noted. The condition comprises three principal subtypes: irritant contact dermatitis, allergic contact dermatitis, and atopic dermatitis.

Gusacitinib has broad inhibitory activity across the JAK signaling pathway, including JAK1, 2, and 3, TYK2, and SYK, he continued. Gusacitinib targets the Th1, Th2, Th17, and Th22 cytokine pathways, as well as SYK-mediated IL-17 signaling in keratinocytes.

Sofen reported findings from the phase IIb randomized trial to evaluate the efficacy, safety, tolerability, and pharmacokinetic profile of gusacitinib in patients with moderate-to-severe chronic hand eczema. The trial included adults with chronic hand eczema of at least 6 months' duration, Physician Global Assessment (PGA) score of 3 or 4, and refractory to moderate, high, or ultra-high potency topical corticosteroids or systemic corticosteroids in the past year.

The trial had two stages. During the first part, patients were randomized to one of two doses of gusacitinib or to placebo and followed for 16 weeks, when assessment of the primary endpoint occurred (percent change in TLSS from baseline). During the second stage, patients assigned to gusacitinib continued their original doses, and placebo-treated patients continued treatment with the 80-mg dose of gusacitinib.

Baseline TLSS averaged 13.0 to 13.5 across the three groups with PGA scores of 12-14, and HECSI of 61-65.

Data analysis comprised 97 patients. Analysis of the primary endpoint showed significant improvement in the 80-mg at all timepoints from week 2 to week 16 (P=0.005). The improvement in TLSS in the 40-mg arm also differed significantly from placebo at 2 weeks (37.6% vs 13.6%, P=0.005). The difference in PGA favored the 80-mg gusacitinib group over placebo from weeks 2-16 (P=0.05 to P=0.005). The 40-mg arm exhibited significantly greater improvement versus placebo at 2 and 4 weeks (P=0.05).

The HECSI analysis showed 72% improvement in the 80-mg arm at week 16 as compared with 20.8% in the placebo arm (P=0.005). The 40-mg gusacitinib group also had significant improvement versus placebo (51.4%, P=0.05).

The advantage of gusacitinib (80 mg and 40 mg) over placebo persisted during follow-up to 32 weeks, following the placebo group's crossover to gusacitinib, said Sofen. The higher dose of gusacitinib improved TLSS versus placebo in the three subtypes of chronic hand eczema versus placebo: hyperkeratotic (72.6% vs 31.2%, P=0.005), vesicular (77.5% vs 50.6%, NS), and fingertip (79.9% vs 27.6%, P<0.01).

Foot eczema, which often accompanies chronic hand eczema, also exhibited significantly greater improvement in TLSS at 16 weeks with gusacitinib 80-mg as compared with placebo (98.4% vs 43.4%, P<0.05). The 40-mg gusacitinib group had a numerical advantage over placebo at all time points. Patient-reported pain decreased by 2.9 points with gusacitinib 80 mg at 16 weeks as compared with 1.38 points with placebo (P<0.05).

With regard to safety, patients treated with gusacitinib had asymptomatic elevations in creatinine phosphokinase, consistent with the JAK inhibitor class, Sofen reported. No opportunistic infections, thromboembolic events, or major adverse cardiovascular events, malignancies, or deaths occurred in gusacitinib-treated patients.

Comment