Deucravacitinib Shows Long-Term Safety, Efficacy in Psoriasis Trial

Deucravacitinib demonstrated a consistent safety profile and durable clinical response through 3 years of treatment in patients with moderate to severe plaque psoriasis, according to a new study.¹

A consistent safety profile and sustained efficacy were observed in patients with moderate to severe plaque psoriasis. | Image Credit: IIIRusya - stock.adobe.com

The integrated analysis of the phase 3 POETYK PSO-1 (NCT03624127), PSO-2 (NCT03611751), and nonrandomized long-term extension (LTE) trials is published in JAMA Dermatology.

“Three-year data represent an important milestone to inform the clinical community regarding the long-term safety and efficacy of a systemic medication,” wrote the researchers of the study. “We present the long-term safety and efficacy of deucravacitinib through a cumulative period of 3 years (PSO-1 and PSO-2 parent trials, 1 year; LTE trial, 2 years).”

Deucravacitinib is an oral, first-in-class selective tyrosine kinase (TYK) 2 inhibitor that modulates key cytokines involved in immune-mediated diseases, including interleukin (IL)-23, IL-12, and type 1 interferons.² Its selectivity stems from allosteric inhibition, targeting the regulatory domain of TYK2 rather than directly inhibiting Janus kinase (JAK) 1, JAK2, or JAK3 at therapeutic doses.

The trial followed patients with moderate to severe plaque psoriasis who had completed 52 weeks of treatment in the POETYK PSO-1 or PSO-2 trials, allowing them to receive open-label deucravacitinib.¹ Safety was the primary outcome, assessed continuously over 3 years, with efficacy as a secondary measure.

Safety evaluations included adverse events (AEs), serious AEs, and specific AEs of interest such as infections, cardiovascular events, and malignancies. Efficacy was measured using Psoriasis Area Severity Index (PASI) 75, PASI 90, and Static Physician's Global Assessment 0/1 scores in patients who received continuous deucravacitinib treatment from day 1.

Statistical analyses included exposure-adjusted incidence rates (EAIRs) to account for treatment duration variations and multiple imputation methods for missing data.

In the as-treated safety population of 1519 patients receiving at least 1 dose of deucravacitinib, 513 patients maintained continuous treatment from day 1 and transitioned into the LTE trial.

Safety outcomes demonstrated stable or decreased EAIRs over time. Comparing the 1-year and 3-year cumulative periods, respectively, EAIRs per 100 person-years declined or remained similar for AEs (229.2 vs 144.8), serious AEs (5.7 vs 5.5), discontinuations due to AEs (4.4 vs 2.4), and deaths (0.2 vs 0.3).

Common AEs such as nasopharyngitis (26.1 vs 11.4) and upper respiratory tract infection (13.4 vs 6.2) showed reduced incidence over time, while COVID-19 cases increased (0.5 vs 8.0) due to the global pandemic. EAIRs for key AEs of interest, including herpes zoster, major adverse cardiovascular events, and malignancies, remained low and stable. Notably, clinical response rates were sustained through 3 years, reinforcing the long-term efficacy and tolerability of deucravacitinib in patients with moderate to severe plaque psoriasis.

The researchers acknowledged some limitations to their findings. The trial included a relatively small study population and a time frame that may not fully capture long-term safety and efficacy outcomes. The researchers believe longer-term results in a larger and more diverse population are needed to further validate these findings and assess the durability of clinical benefits and risk profiles over extended periods.

Despite these limitations, the researchers believe the findings indicate that AEs remained low or decreased over time, supporting the use of deucravacitinib.

“These findings provide additional support for deucravacitinib as an efficacious and well-tolerated, long-term treatment for patients with moderate to severe plaque psoriasis,” wrote the researchers.

References

1. 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. 2025;161(1):56-66. doi:10.1001/jamadermatol.2024.4688

2. Hebebrand M. Phase 3 trials confirm deucravacitinib’s efficacy in PsA. Dermatology Times^®. December 24, 2024. Accessed February 12, 2025. https://www.dermatologytimes.com/view/phase-3-trials-confirm-deucravacitinib-s-efficacy-in-psa