Deucravacitinib Effective in Patients with Cutaneous Lupus, Including Concurrent SLE

Deucravacitinib therapy may be a promising treatment option for those with cutaneous lupus, new findings suggest, including those with concurrent subacute cutaneous lupus erythematosus (SCLE).1

The PAISLEY CLE trial findings were released in a poster at the Dermatology Education Foundation (DERM) 2025 NP/PA CME Conference in Las Vegas, in a poster titled 'Efficacy and Safety of Deucravacitinib in Patients With Discoid Lupus Erythematosus (DLE) and/or Subacute Cutaneous Lupus Erythematosus (SCLE): Results From PAISLEY CLE, a Global, Phase 2 Randomized, Double-blind, Placebo-Controlled Trial.'

The phase 2, randomized, placebo-controlled, double-blind study was designed to assess deucravacitinib, a first-in-class, oral, selective allosteric inhibitor of tyrosine kinase 2 (TYK2). The research specifically looked at patients living with active discoid lupus erythematosus (DLE) and/or SCLE, with or without coexisting systemic lupus erythematosus (SLE).

Deucravacitinib, which is already approved by regulatory bodies for moderate to severe psoriasis in a variety of countries, had previously demonstrated efficacy across multiple clinical endpoints in those with SLE during the PAISLEY analysis. In the current study, the investigative team sought to build on those results by targeting cutaneous lupus manifestations specifically and included those living with and without systemic involvement, capping SLE cases at 50% of the trial population.

The study was authored by such investigators as Victoria P. Werth MD, Professor of Dermatology at the Hospital of the University of Pennsylvania and the Veteran's Administration Medical Center. Werth et al determined eligible adult subjects would have had a histologically confirmed diagnosis of moderate to severe DLE or SCLE.

These conditions were defined by Werth and coauthors as a baseline Cutaneous Lupus Erythematosus Disease Area and Severity Index activity (CLASI-A) score of 8 or higher. Seventy-four individuals were enrolled and randomized in a 1:1:1 ratio to be given either a placebo, deucravacitinib 3 mg twice-per-day, or deucravacitinib 6 mg twice-daily for 16 weeks.

After this period, those initially assigned to placebo were re-randomized to 1 of the 2 deucravacitinib doses for the remainder of the study's 52-week treatment timeframe. Meanwhile, participants already on active therapy continued their assigned drug regimens. Werth and colleagues' primary endpoint focused on the mean percent change from baseline in CLASI-A score at the 16-week mark.

In terms of secondary and exploratory endpoints, examples included attainment of a 50% or greater CLASI-A (CLASI-50) improvement, a 70% or greater improvement (CLASI-70), the trajectory of CLASI-A score improvement over time, and levels patient-reported skin pain via visual analog scale. Notably, this phase 2 study used a 2-sided alpha level of .10 to determine statistical significance, without adjustments for several different comparisons.

Overall, Werth et al's research met its primary endpoint, with patients receiving deucravacitinib leading to significantly greater CLASI-A score improvements compared to placebo.1 Specifically, mean percent reductions in CLASI-A scores were −47.5% and −50.0% for the 3 mg and 6 mg doses, respectively, versus −28.4% in the placebo cohort. The P-values for these differences were .0670 and .0385, respectively, indicating statistical significance at the predetermined threshold. Similarly, absolute changes in CLASI-A scores also favored those in the deucravacitinib arms, with greater reductions from baseline observed by the investigators compared to placebo.

By the 16-week mark, Werth and colleagues concluded that more than half of those given either dose attained CLASI-50, and this was compared to just 19% of those in the placebo arm. Rates of CLASI-70 responses were also shown to be higher with this medication, particularly for the 3 mg dose, which reached statistical significance. Skin pain improvements were noted by the investigative team as well, though these were described numerically rather than statistically.

Notably, benefits from the therapy emerged as early as the 4-week mark and tended to persist through the full 52 weeks of this analysis. Deucravacitinib was shown to generally be well tolerated. Werth et al identified no new safety concerns, and adverse events (AEs) were mostly mild to moderate in their level of severity. Among the most reported events, examples included headaches, upper respiratory infections, and acneiform dermatitis. The investigators also highlighted a lack of discontinuations due to AEs.

They also pointed out that no reports of serious complications such as herpes zoster, venous thromboembolism, cardiovascular events, malignancy, or opportunistic infections were seen. Laboratory parameters also were noted as having remained stable, with a lack of clinically meaningful abnormalities across treatment cohorts in the analysis.

In summary, deucravacitinib provide a promising medication option for those living with cutaneous lupus, including patients with concurrent SLE. Its favorable safety profile and significant clinical improvements support ongoing development, including the continued assessment of the drug in the phase 3 POETYK SLE trials.

References

1. Werth V, Gottlieb A, Merola J, et al. Efficacy and Safety of Deucravacitinib in Patients With Discoid Lupus Erythematosus (DLE) and/or Subacute Cutaneous Lupus Erythematosus (SCLE): Results From PAISLEY CLE, a Global, Phase 2 Randomized, Double-blind, Placebo-Controlled Trial. Presented at DERM 2025 NP PA CME Conference; July 23-26, 2025; Las Vegas, Nevada.