Four-Year Efficacy & Safety of Deucravacitinib in Plaque Psoriasis

New four-year data from the long-term extension (LTE) of the Phase 3 POETYK PSO-1 and PSO-2 trials provide updated insight into the use of deucravacitinib in adults with moderate-to-severe plaque psoriasis. As the first and only approved TYK2 inhibitor acting allosterically on the regulatory domain, deucravacitinib demonstrates sustained efficacy and a stable safety profile over four years of continuous treatment.

Sustained Efficacy Across Key Endpoints
Among the 1,519 patients who received at least one dose of deucravacitinib, 513 were in the efficacy population and treated continuously from day 1 of the parent trials through week 208. Clinical response rates remained stable across key efficacy endpoints. At four years:

• PASI 75 was achieved by 71.7% (vs. 72.0% at Year 1)
• PASI 90 by 47.5% (vs. 45.6%)
• PASI 100 by 21.2% (vs. 20.1%)
• sPGA 0/1 by 57.2% (vs. 57.7%)
• ss-PGA 0/1 (scalp) responses were sustained, while PGA-F 0/1 (nails) responses improved over time.

The magnitude and durability of response are particularly notable in traditionally recalcitrant areas, like the scalp and fingernails.

No New Safety Signals Over 4,400 Person-Years of Exposure
Across a cumulative exposure of 4,392.8 person-years, the overall safety findings remained consistent with earlier results:

• Overall adverse event (AE) rate: 131.7 per 100 person-years (PY)
• Serious adverse events (SAEs): 5.0 per 100 PY
• AE-related discontinuations: 2.2 per 100 PY
• Herpes zoster: 0.55 per 100 PY
• Malignancies (excluding nonmelanoma skin cancer): 0.50 per 100 PY
• Major adverse cardiovascular events (MACE): 0.32 per 100 PY
• Venous thromboembolism (VTE): 0.07 per 100 PY

The majority of serious infections during the long-term extension were COVID-19 related, and incidence rates excluding COVID-19 declined over time (1-year: 1.53/100 PY; 4-year: 0.80/100 PY).

Notably, laboratory values—including hematologic, liver enzyme, creatinine, and lipid panels—remained within normal limits for the majority of patients throughout the study duration, and no JAK-like lab signal was observed.

Consistent Patient-Reported Outcomes
Patient assessments through the Psoriasis Symptoms and Signs Diary (PSSD) and DLQI scores showed sustained improvement:

• DLQI 0/1 rates were 51.5% at Year 1 and 49.4% at Year 4
• Mean DLQI improvement from baseline: –8.5
• PSSD total score reduction: –32.2 (Week 196, MI-BOCF analysis).

These scores suggest a consistent patient-perceived benefit over time, though interpretation should take into account the potential for response bias in LTEs.

Clinical Considerations
These results contribute to the growing body of evidence on deucravacitinib’s long-term performance. For individuals with moderate-to-severe plaque psoriasis who are eligible for systemic therapy, the data may inform shared decision-making regarding treatment durability and safety. Deucravacitinib’s oral administration may be a consideration for patients preferring alternatives to injectable biologics or seeking therapies target an alternative immunomodulatory pathway.

In terms of safety, rates of key events such as MACE, malignancies, and serious infections appear consistent with long-term findings from other systemic agents used in psoriasis. These include IL-12/23 and IL-17 inhibitors, though direct comparisons are limited.

Given the need for long-term management strategies in chronic inflammatory diseases, deucravacitinib’s evolving evidence base may help close a therapeutic gap between traditional orals and biologics.

Reference

Armstrong AW, Lebwohl M, Warren RB, et al. Deucravacitinib in plaque psoriasis: Four-year safety and efficacy results from the Phase 3 POETYK PSO-1, PSO-2 and long-term extension trials. J Eur Acad Dermatol Venereol. 2025;00:1-16. https://doi.org/10.1111/jdv.20553