Deucravacitinib in plaque psoriasis: Safety and efficacy through 3 years in Japanese patients in the phase 3 POETYK PSO-1, PSO-4, and LTE trials

Abstract

Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, was effective and well tolerated at a dose of 6 mg once daily through 1 year (52 weeks) in patients with moderate to severe plaque psoriasis in the phase 3 POETYK PSO-1 and POETYK PSO-4 trials. Patients completing PSO-1 or PSO-4 could enter the ongoing POETYK long-term extension trial and receive open-label deucravacitinib. Safety and efficacy were evaluated through 3 years (148 weeks; data cutoff date: June 15, 2022) in Japanese patients in these trials. Safety was assessed via adverse events (AEs). Efficacy endpoints, including ≥75% reduction from baseline in the Psoriasis Area and Severity Index (PASI 75) and static Physician Global Assessment (sPGA) score of 0/1 (clear/almost clear), were evaluated in patients receiving continuous deucravacitinib treatment from baseline in PSO-1 and PSO-4 and in PSO-1 patients crossing over from placebo to deucravacitinib at week 16. At data cutoff, 125 patients had received at least one deucravacitinib dose; 86.4% had >24 months and 27.2% had >36 months of total deucravacitinib exposure. Exposure-adjusted incidence rates per 100 person-years for AEs were: any AEs, 188.5; discontinuations attributable to AEs, 3.2; serious AEs, 7.4; serious infections, 1.3; herpes zoster events, 1.6; major adverse cardiovascular events, 0.6; venous thromboembolic events, 0; and malignancies, 1.0. Clinical responses (as observed) were maintained in PSO-1 patients receiving continuous deucravacitinib treatment from baseline (PASI 75: year 1, 88.9%; year 3, 87.5%; sPGA 0/1: year 1, 74.1%; year 3, 66.7%). Year 1 response rates were also maintained through year 3 in PSO-4 patients and in PSO-1 placebo crossovers. Response rates were also consistent using modified nonresponder imputation and treatment failure rules data imputation methodologies. These findings support the consistent safety profile and durable efficacy of deucravacitinib through 3 years in Japanese patients with psoriasis. ClinicalTrials.gov: NCT03624127; NCT03924427; NCT04036435.

Keywords: long‐term; phase 3; psoriasis; safety; tyrosine kinase 2 inhibitor.

FIGURE 1

The designs of the POETYK PSO‐1, PSO‐4, and long‐term extension (LTE) studies, which include Japanese patients who received at least one dose of deucravacitinib 6 mg once daily (QD). The study design of PSO‐1 in the global population has been previously described.^{17 †}Apremilast was titrated from 10 mg QD to 30 mg twice daily (BID) during the first 5 days of dosing. ^‡Data reported through 3 years (data cutoff date: June 15, 2022). PASI 50/75, ≥50%/≥75% reduction from baseline in Psoriasis Area and Severity Index; sPGA 0/1, static Physician Global Assessment score of 0 (clear) or 1 (almost clear) with a ≥2‐point improvement from baseline.

FIGURE 2

Creatine phosphokinase (CPK) levels through 3 years in Japanese patients with plaque psoriasis in the pooled POETYK PSO‐1, PSO‐4, and long‐term extension trials. In PSO‐1, a 35‐year‐old Asian man had a grade 4 CPK elevation (14 707 U/L) at week 8 and a 30‐year‐old Asian man had a grade 3 CPK elevation (2451 U/L) at week 24; both events had resolved during subsequent visits on continued treatment with deucravacitinib. All other CPK elevations were grade ≤2 (≤1283 U/L).

FIGURE 3

Efficacy is reported through 3 years in Japanese patients with plaque psoriasis receiving continuous deucravacitinib treatment in POETYK PSO‐1. ^†Treatment failure rule (TFR) analysis captures discontinuations coded as “lack of efficacy” or “worsening of psoriasis.” ^‡Modified nonresponder imputation (mNRI) analysis captures discontinuations coded as “worsening of psoriasis.” Data callouts represent the response rate (95% confidence interval]). LTE, long‐term extension; PASI 75/90/100, ≥75%/≥90%/100% reduction from baseline in Psoriasis Area and Severity Index; sPGA 0/1, static Physician Global Assessment score of 0 (clear) or 1 (almost clear) with ≥2‐point improvement from baseline.[Correction added on 18 April 2025 after first online publication: The legend of figure 3 has been modified.]

FIGURE 4

Efficacy is reported through 3 years in Japanese patients with plaque psoriasis crossing over from placebo to deucravacitinib at week 16 in POETYK PSO‐1. ^†Treatment failure rule (TFR) analysis captures discontinuations coded as “lack of efficacy” or “worsening of psoriasis.” ^‡Modified nonresponder imputation (mNRI) analysis captures discontinuations coded as “worsening of psoriasis.” Data callouts represent the response rate (95% confidence interval). LTE, long‐term extension; PASI 75/90/100, ≥75%/≥90%/100% reduction from baseline in Psoriasis Area and Severity Index; sPGA 0/1, static Physician Global Assessment score of 0 (clear) or 1 (almost clear) with ≥2‐point improvement from baseline.

FIGURE 5

Efficacy is reported through 3 years in Japanese patients with plaque psoriasis in POETYK PSO‐4. ^†Treatment failure rule (TFR) analysis captures discontinuations coded as “lack of efficacy” or “worsening of psoriasis.” ^‡Modified nonresponder imputation (mNRI) analysis captures discontinuations coded as “worsening of psoriasis.” Data callouts represent the response rate (95% confidence interval). LTE, long‐term extension; mNRI, modified nonresponder imputation; PASI 75/90/100, ≥75%/≥90%/100% reduction from baseline in Psoriasis Area and Severity Index; sPGA 0/1, static Physician Global Assessment score of 0 (clear) or 1 (almost clear) with ≥2‐point improvement from baseline.