A recent study published in Annals of the Rheumatic Diseases found that deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, demonstrated superior efficacy across multiple clinical and patient-reported outcomes, inhibited structural damage progression, and had a favourable safety profile through 52 weeks in biologic disease-modifying antirheumatic drug-naïve patients with active psoriatic arthritis (PsA).
There remains an unmet need for oral treatments that are safe, well tolerated, and effective across multiple domains of psoriatic arthritis (PsA), including musculoskeletal and skin manifestations, as well as structural damage, quality of life, pain, and physical function. Tyrosine kinase 2 (TYK2) modulates the downstream effects of immune-mediating cytokines involved in PsA pathophysiology, including interleukin (IL)-23, IL-12, and type I interferons. The unique binding mechanism of deucravacitinib confers selectivity for TYK2 over Janus kinases 1, 2, and 3. Deucravacitinib is the first agent in a new class of oral TYK2 inhibitors under investigation for the treatment of active PsA.
The randomised, double-blind, placebo-controlled, phase 3 POETYK PsA-1 trial evaluated the efficacy, safety, and tolerability of deucravacitinib in adults with active PsA, high-sensitivity C-reactive protein concentration ≥3 mg/L, and at least one PsA-related hand and/or foot erosion detectable via radiograph. A total of 670 patients were randomised 1:1 to oral deucravacitinib 6 mg once daily or placebo through week 16. At week 16, patients continued receiving deucravacitinib or switched from placebo to deucravacitinib through week 52. The primary endpoint was American College of Rheumatology 20% improvement response (ACR20) at week 16. Missing data were handled using nonresponder imputation, while post hoc rank analysis of covariance was used to evaluate structural damage without missing data imputation.
At week 16, a significantly greater proportion of patients receiving deucravacitinib achieved ACR20 compared with placebo (54.2% vs 34.1%; P < .001). Responses with deucravacitinib increased at week 52, and patients who switched from placebo to deucravacitinib achieved improvements similar to those observed in patients receiving continuous deucravacitinib. Inhibition of structural damage was observed at weeks 16 and 52. At week 16, serious adverse events occurred in 1.8% of patients receiving deucravacitinib and 2.4% receiving placebo, while discontinuations due to adverse events occurred in 2.4% and 1.8%, respectively. These incidences remained low through week 52, without imbalances in cardiovascular events, malignancies, or opportunistic infections. No new safety signals were detected, and no deaths occurred. Approximately 80% of patients completed study treatment through week 52.
The study supported the efficacy of deucravacitinib across multiple PsA domains, including overall disease activity, joint and skin clinical responses, pain, fatigue, and health-related quality of life, while its inhibition of structural damage progression suggested a potential role for TYK2 inhibition in limiting radiographic progression.
Reference
van der Heijde D, Mease PJ, Paul C, Behrens F, Gossec L, Kaneko Y, et al. Efficacy and safety of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with active psoriatic arthritis: 52-week results from the randomised, double-blind, placebo-controlled phase 3 POETYK PsA-1 trial. Ann Rheum Dis. 2026 Sep;85(9):1729-1742