Deucravacitinib: Long-term safety and efficacy reaffirm its place in the psoriasis treatment landscape

Abstract

Deucravacitinib is an oral, highly selective TYK2 inhibitor approved for the treatment of moderate to severe plaque psoriasis.^{1, 2} A key aspect that differentiates this allosteric inhibitor from other oral immunomodulators is its selective binding to the regulatory domain of TYK2, avoiding inhibition of JAK1, JAK2 and JAK3. This selectivity enables targeted modulation of IL-12, IL-23 and type I interferon pathways, resulting in a distinct and potentially more favorable safety profile.^{1, 2}

Armstrong et al.¹ present 4-year results from the POETYK PSO-1, PSO-2 and their long-term extension trials, offering key insights into the durability of deucravacitinib's efficacy and safety. Given the chronic, immune-mediated nature of psoriasis, such findings are particularly relevant as they highlight the need for durable systemic treatment options.

The data are encouraging¹ – patients treated continuously with deucravacitinib maintained stable PASI 75 (72.0% at year one vs. 71.7% at year four) and PASI 90 response rates (45.6% at year one vs. 47.5% at year four) over 4 years. Nearly half of patients achieved DLQI 0/1, indicating minimal or no impact on their quality of life. Importantly, the safety outcomes remained stable throughout the 4393 patient-years of exposure, with low and consistent rates of serious infections, malignancies, major cardiovascular events and venous thromboembolism. Notably, no new safety concerns emerged and discontinuations due to adverse events decreased over time.

Certain limitations, however, must be considered. As an open-label extension, the study inherently includes a responder bias, as participants who did not benefit or tolerate treatment in the initial phase likely discontinued. Moreover, the apremilast arm was discontinued after year 1, preventing direct long-term comparisons of efficacy and safety against other therapies, including newer biologics and oral agents.

Despite these limitations, Armstrong et al. provide robust evidence supporting deucravacitinib's role as a reliable long-term oral therapy for moderate to severe psoriasis. Importantly, in contrast to other JAK inhibitors, deucravacitinib has not been subject to a black box warning by the FDA. This is significant, particularly considering FDA concerns surrounding cardiovascular and malignancy risks with JAK1/2/3 inhibitors. The presented 4-year data thereby further reinforce the benefits of TYK2 selectivity.

The February 2025 update of the EuroGuiDerm guideline nevertheless recommends monitoring full blood count, liver enzymes, creatine phosphokinase and lipid profile where clinically indicated, every 3–6 months during treatment and advises treatment interruption if myopathy or liver injury is suspected.³ Reassuringly, the 4-year data did not show clinically meaningful changes from baseline in terms of laboratory tests, consistently supporting the safety profile.¹

Recent literature also affirms that TYK2 inhibitors may combine the convenience of oral administration with an improved long-term benefit–risk profile compared to less selective JAK inhibitors (Shah et al. 2025 J Drugs Dermatol.).⁴ Patient surveys further emphasize that efficacy, safety and oral administration are key factors in treatment choice, particularly in chronic diseases like psoriasis (Armstrong et al. 2024 Dermatol Ther Heidel).⁵

Although the 4-year data attest to deucravacitinib's sustained efficacy and favourable safety profile, the mentioned limitations call for caution in interpreting these outcomes as definitive safety advantages. Its positioning among systemic psoriasis therapies will require further head-to-head comparisons with newer oral agents and biologics, as well as results from long-term real-world evidence studies. However, the current data suggest it is a well-tolerated oral option that provides long-lasting efficacy with potentially reduced safety risks associated with broader immunosuppression.

In summary, the long-term analysis from Armstrong et al. supports deucravacitinib's potential as a durable, safe and patient-friendly treatment for moderate to severe plaque psoriasis. From a clinician's perspective, such a well-tolerated oral therapy with sustained disease control is an encouraging addition to existing therapies—especially for patients who value the convenience of an oral treatment.

IB is an employee of the University Hospital of Zurich and PhD candidate at the University of Zurich and has declared no conflict of interest. SSS has received speaking fees and/or travel support from Abbvie, Janssen, Novartis and UCB, outside the submitted work. JTM has served as advisor and/or received speaking fees and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, BMS, Celgene, Eli Lilly, Incyte, LEO Pharma, Janssen-Cilag, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi and UCB.