Deucravacitinib Demonstrates Significantly Greater PASI Reductions in Plaque Psoriasis

Mark Lebwohl, MD

Credit: Arcutis

Patients with moderate to severe plaque psoriasis treated with deucravacitinib achieved clinically meaningful and treat-to-target absolute Psoriasis Area and Severity Index (PASI), according to data presented at the 2023 Fall Clinical Dermatology Conference.¹ Significantly great improvements were shown in patients receiving deucravacitinib when compared with those receiving placebo to week 16 and apremilast to week 24, and improvements were maintained through 52 weeks.

The drug, an oral, selective allosteric tyrosine kinase 2 (TYK2) inhibitor, is currently approved for the treatment of adults with moderate to severe plaque psoriasis. It works by binding to the regulatory domain of TYK2, as opposed to the catalytic domain of Janus kinase (JAK) inhibitors.

“Treatment outcomes for plaque psoriasis based on the absolute PASI scores achieved are indicative of a patient’s disease severity at the time of analysis,” wrote a team of investigators led by Mark Lebwohl, MD, Icahn School of Medicine at Mount Sinai. “Achieving absolute PASI thresholds may be more clinically meaningful and relevant in clinical settings than achieving a set percent reduction from baseline in PASI captured by scores such as PASI 75 (≥75% reduction from baseline in PASI).”

Additionally, previous research has shown an absolute PASI ≤2 is indicative of meaningful improvements in both clinical and health-related quality of life (HRQoL) outcomes and an absolute PASI ≤3 should be a treatment goal for patients with psoriasis.

POETYK PSO-1 and POETYK PSO-2 were global, phase 3, double-blind trials evaluating the efficacy of deucravacitinib compared with either placebo or apremilast using mean PASI improvements from baseline. Investigators also assessed absolute PASI thresholds with continuous deucravacitinib treatment through 1 year in POETYK PSO-1.

Eligible patients were adults (aged ≥18 years) with moderate to severe plaque psoriasis, as defined by a baseline PASI ≥12, body surface area (BSA) involvement of ≥10%, and a static Physician Global Assessment (sPGA) ≥3. Patients were randomized 1:2:1 to placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily, respectively. The randomization was stratified by previous biologic use, body weight, and geographic region.

The mean outcomes were the percent change from baseline in PASI scores using a modified baseline-observation-carried-forward approach, the proportions of patients who achieved absolute pre-determined PASI thresholds using nonresponder imputation (NRI).

Both trials demonstrated significantly more improvement in the deucravacitinib group when compared with the placebo and apremilast cohorts. A significantly higher proportion of patients in the deucravacitinib cohort were able to achieve the treat-to-target thresholds of absolute PASI ≤1, ≤2, ≤3, ≤4, and ≤5 at the 52-week mark. Those receiving deucravacitinib alswo had significantly greater mean reduction from baseline in PASI compared with placebo (-68.1 vs -21.0%, respectively) and apremilast (-68.1 vs 47.0%, respectively). Additionally, patients receiving treatment with continuous deucravacitinib were able to maintain mean reduction in PASI scores through week 52 (-78.4%).

“These findings suggest that deucravacitinib, an oral, once-daily drug, has the potential to become a treatment of choice for patients with moderate to severe plaque psoriasis,” investigators concluded.

References

1. ^{Lebwohl M, Gooderham M, Warren RB, Thaci D, et al. Deucravacitinib, an oral, selective allosteric tyrosine kinase 2 inhibitor, in moderate to severe plaque psoriasis: absolute PASI outcomes over 52 weeks in the phase 3 POETYK PSO-1 trial. Presented at: Fall Clinical Dermatology 2023 Conference. Las Vegas, NV. October 19 – 22, 2023.}