PACULit Daily Literature Update
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
Morita A, Imafuku S, Tada Y, et al. J Dermatol. 2025;52(5):761-772. doi:10.1111/1346-8138.17685.
Introduction
Moderate to severe plaque psoriasis is a chronic inflammatory skin condition that significantly impacts patients’ quality of life. Treatment options that provide durable efficacy with a favorable safety profile are essential for long-term disease management, especially in specific populations such as Japanese patients, who may exhibit distinct clinical characteristics and treatment responses.
Deucravacitinib, an oral selective allosteric tyrosine kinase 2 (TYK2) inhibitor, has emerged as a promising therapeutic agent. This report summarizes the comprehensive 3-year safety and efficacy data from the phase 3 POETYK PSO-1, PSO-4, and long-term extension (LTE) trials focusing on Japanese patients.
Study Overview
Study Type: Phase 3 randomized controlled trials (POETYK PSO-1, PSO-4) with open-label LTE extension
Population: 125 Japanese patients with moderate to severe plaque psoriasis
Intervention: Deucravacitinib 6 mg orally once daily
Duration: Up to 3 years (148 weeks), data cutoff June 15, 2022
Outcomes: Safety assessed by adverse events (AEs) incidence rates; efficacy assessed by PASI 75 response and static Physician Global Assessment (sPGA) 0/1 (clear/almost clear) scores.
Efficacy was evaluated in patients continuously treated with deucravacitinib from baseline in PSO-1 and PSO-4, as well as in PSO-1 patients who crossed over from placebo to deucravacitinib at week 16.
Key Findings
- 125 Japanese patients received at least one dose; 86.4% had >24 months exposure, 27.2% had >36 months exposure.
- Exposure-adjusted incidence rates (per 100 person-years): any AEs 188.5; discontinuations due to AEs 3.2; serious AEs 7.4; serious infections 1.3; herpes zoster 1.6; major adverse cardiovascular events (MACE) 0.6; venous thromboembolic events (VTE) 0; malignancies 1.0.
- Two patients experienced grade 3 or 4 creatine phosphokinase (CPK) elevations; both resolved without treatment discontinuation.
- Clinical efficacy was durable: PASI 75 response rates for continuous deucravacitinib patients were 88.9% at year 1 and 87.5% at year 3; sPGA 0/1 rates were 74.1% at year 1 and 66.7% at year 3.
- Similar durable responses observed in PSO-4 patients and PSO-1 placebo crossovers.
- Response consistency confirmed using modified nonresponder imputation (mNRI) and treatment failure rules (TFR) methodologies.
Evidence Synthesis & Clinical Context
The long-term safety and efficacy findings by Morita et al. align with the broader POETYK clinical trial program, which includes global and Japanese-specific cohorts.
Global POETYK Program
- The 52-week POETYK PSO-1 trial demonstrated deucravacitinib’s superiority over placebo and apremilast in a global population, including Japanese patients (Armstrong et al., 2023).
- The POETYK PSO-4 trial confirmed efficacy and safety specifically in Japanese patients through 52 weeks (Okubo et al., 2024).
- An integrated analysis of the global POETYK program showed maintained clinical responses and stable safety profiles over 3 years in international populations (Armstrong et al., 2024).
Population Differences and Data Nuances
- Adverse event rates differ numerically between Japanese-specific and global integrated analyses, reflecting population scope differences.
- Consistent themes include foundational 52-week efficacy and safety, with durable responses maintained through 3 years.
- Evidence gaps remain due to lack of long-term active comparator data and absence of direct statistical comparisons between Japanese and non-Japanese subgroups.
Evidence Integration
Collectively, these data support deucravacitinib as a well-tolerated, effective long-term oral therapy for moderate to severe plaque psoriasis, with a consistent safety profile and durable efficacy in Japanese patients, consistent with global findings.
Clinical Implications
- Deucravacitinib 6 mg once daily offers sustained efficacy and a favorable safety profile for up to 3 years in Japanese patients with moderate to severe plaque psoriasis.
- Long-term data from open-label extension studies enhance confidence in its use as a durable oral treatment option.
- Clinicians should consider deucravacitinib as a viable long-term therapy, while recognizing the absence of long-term active comparator data.
Strengths & Limitations
| Strengths | Limitations |
|---|---|
| Robust 3-year follow-up with high patient retention (86.4% >24 months exposure) | Open-label LTE design may introduce bias in long-term assessments |
| Comprehensive safety assessment with exposure-adjusted incidence rates | Lack of long-term active comparator arm limits direct efficacy comparisons |
| Consistent efficacy assessment using multiple imputation methods (mNRI, TFR) | Relatively small Japanese cohort may limit generalizability to broader populations |
Future Directions
Further research is needed to evaluate long-term comparative efficacy against active treatments beyond 52 weeks and to explore potential differences in treatment response between Japanese and non-Japanese populations through direct statistical analyses.
Conclusion
Deucravacitinib demonstrates a favorable safety profile and durable efficacy over 3 years in Japanese patients with moderate to severe plaque psoriasis, supporting its long-term use in this population.
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References
- Morita A, Imafuku S, Tada Y, et al. 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. J Dermatol. 2025;52(5):761-772. doi:10.1111/1346-8138.17685.
- Armstrong AW, Lebwohl M, Warren RB, et al. Safety and Efficacy of Deucravacitinib in Moderate to Severe Plaque Psoriasis for Up to 3 Years: An Open-Label Extension of Randomized Clinical Trials. JAMA Dermatol. 2024;161(1):56-66.
- Armstrong AW, Gooderham M, Warren RB, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 POETYK PSO-1 trial. Br J Dermatol. 2023;188(1):29-39.
- Okubo Y, Morita A, Imafuku S, et al. Deucravacitinib, an Oral, Selective, Allosteric Tyrosine Kinase 2 Inhibitor, in Japanese Patients With Plaque Psoriasis: In-Depth Analysis of Efficacy and Safety in the Phase 3 POETYK PSO-4 Trial. J Dermatol. 2024;52(6):953-966.
