Deucravacitinib in plaque psoriasis: Four-year safety and efficacy results from the Phase 3 POETYK PSO-1, PSO-2 and long-term extension trials

Deucravacitinib in plaque psoriasis: Four-year safety and efficacy results from the Phase 3 POETYK PSO-1, PSO-2 and long-term extension trials

Armstrong AW, Lebwohl M, Warren RB, et al. J Eur Acad Dermatol Venereol. 2025;39(7):1336-1351. doi:10.1111/jdv.20553. PMID:40045918.

Introduction

Moderate to severe plaque psoriasis is a chronic inflammatory skin condition that significantly impairs quality of life and requires long-term management strategies. Deucravacitinib, an oral, selective allosteric inhibitor of tyrosine kinase 2 (TYK2), has emerged as a promising systemic therapy, already approved in multiple countries for this indication.

This comprehensive analysis reports the four-year safety and efficacy outcomes from the Phase 3 POETYK PSO-1, PSO-2, and long-term extension (LTE) trials, providing critical insights into the durability of clinical benefit and long-term tolerability of deucravacitinib in adults with moderate to severe plaque psoriasis.

Study Overview

Study Design: Phase 3 randomized controlled trials (POETYK PSO-1 and PSO-2) with a subsequent open-label long-term extension (LTE) study.

Population: Adults with moderate to severe plaque psoriasis; initial randomization of 1,519 patients to placebo, deucravacitinib 6 mg once daily (QD), or apremilast 30 mg twice daily.

Intervention: Deucravacitinib 6 mg QD administered orally; patients in LTE received open-label deucravacitinib 6 mg QD after 52 weeks.

Outcomes: Safety assessed in all patients receiving at least one dose of deucravacitinib (n=1,519) with cumulative exposure of 4,392.8 person-years; efficacy assessed in patients continuously treated with deucravacitinib from Day 1 and enrolled in LTE (n=513), using PASI, PGA, and DLQI scores.

Data Cut-off: November 1, 2023.

Key Findings

• Exposure-adjusted incidence rates (EAIRs) per 100 person-years for adverse events (AEs) decreased from 229.23 at 1 year to 131.68 at 4 years.
• Serious AEs, including COVID-19, decreased from 5.68 to 5.01 per 100 PY over 4 years.
• Discontinuations due to AEs declined from 4.38 to 2.20 per 100 PY.
• Incidence of herpes zoster decreased from 0.81 to 0.55 per 100 PY; malignancies from 1.02 to 0.89; venous thromboembolism from 0.20 to 0.07.
• Major adverse cardiovascular events (MACE) remained low and stable: 0.30 at 1 year and 0.32 at 4 years.
• Deaths were rare and stable: 0.20 at 1 year and 0.25 at 4 years.
• Clinical efficacy was durable: PASI 90 response rates were 45.6% at 1 year and 47.5% at 4 years; DLQI 0/1 response rates were 51.5% at 1 year and 49.4% at 4 years.

Evidence Synthesis & Clinical Context

The Armstrong et al. (2025) study represents the most extensive long-term evaluation of deucravacitinib in plaque psoriasis, confirming a consistent safety profile and sustained efficacy over four years. This study builds on prior reports from the same trial program, which demonstrated stable or decreasing adverse event rates at two and three years, reinforcing the drug’s tolerability.

Supporting Literature

• Armstrong et al., 2025: Open-label extension data up to 3 years showed stable safety and efficacy outcomes (JAMA Dermatol. 2025;161(1):56-66).
• Lebwohl et al., 2024: Two-year results from POETYK trials confirmed low incidence of serious AEs and maintained clinical responses (Br J Dermatol. 2024;190(5):668-679).
• Merola et al., 2025: Analysis of adverse events of interest across Phase 3 trials highlighted low rates of serious infections, malignancies, and cardiovascular events (Dermatol Ther. 2025;15(2):453-462).
• Bang et al., 2025: Narrative review discussing deucravacitinib’s expanding therapeutic potential beyond psoriasis, including psoriatic arthritis and systemic lupus erythematosus (J Clin Med. 2025;14(5):1745).
• Tan et al., 2025: Real-world safety evaluation using FDA adverse event reporting system data underscored the importance of ongoing pharmacovigilance (Int J Clin Pharm. 2025;47(4):815-824).

Clinical Implications

• Deucravacitinib demonstrates a favorable long-term safety profile, supporting its use as a chronic systemic therapy for moderate to severe plaque psoriasis.
• Durable efficacy with sustained PASI 90 and DLQI 0/1 responses over four years indicates consistent disease control and quality of life improvement.
• Low and stable rates of serious adverse events, including cardiovascular events and malignancies, support ongoing treatment adherence and patient monitoring strategies.
• Clinicians should consider deucravacitinib as a well-tolerated oral option in the therapeutic armamentarium for plaque psoriasis, with long-term data reassuring safety and efficacy.

Strengths & Limitations

Future Directions

Further real-world studies and post-marketing surveillance are essential to confirm long-term safety and identify rare adverse events. Additionally, research into deucravacitinib’s efficacy and safety in other inflammatory conditions such as psoriatic arthritis and systemic lupus erythematosus is ongoing and may expand its clinical utility.

Conclusion

Deucravacitinib demonstrates a consistent safety profile and durable efficacy over four years of treatment in moderate to severe plaque psoriasis, supporting its role as a long-term oral systemic therapy.

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