Deucravacitinib delivers superior efficacy, safety in active PsA

Deucravacitinib exhibits superiority over placebo in terms of overall disease activity measures, musculoskeletal and dermatologic manifestations, and quality of life in adults with active psoriatic arthritis (PsA) who are naïve to biologic disease-modifying antirheumatic drugs (DMARDs), according to the results of the POETYK PsA-1 study.

“Deucravacitinib, the first oral tyrosine kinase 2 inhibitor evaluated in a phase III trial of PsA, demonstrates the potential to be an efficacious and well-tolerated oral treatment in PsA,” said lead author Dr Desiree van der Heijde from the Department of Rheumatology, Leiden University Medical Centre, Leiden, Netherlands, in her presentation at EULAR 2025.

A total of 670 patients with PsA were randomized in this trial, of whom 336 received deucravacitinib 6 mg QD, while 334 received placebo. Demographics and baseline disease characteristics were balanced between the two treatment groups. [EULAR 2025, abstract LB0001]

Efficacy

At week 16, a significantly higher proportion of patients treated with deucravacitinib vs placebo achieved ACR20 (54.2 percent vs 34.1 percent; p<0.0001), with comparable results for ACR50 (24.7 percent vs 13.5 percent; p=0.0002) and ACR70 (11.6 percent vs 5.4 percent; p=0.0039).

Consistent ACR20 responses were noted, regardless of concomitant use of conventional synthetic DMARDs or high-sensitivity C-reactive protein (CRP) level at baseline.

Deucravacitinib also showed greater efficacy for other endpoints when compared with placebo: Health Assessment Questionnaire Disability Index (‒0.39 vs ‒0.22; p<0.0001), Psoriasis Area and Severity Index 75 (51.9 percent vs 7.1 percent; p<0.0001), Short Form-36 Health Survey Physical Component Summary (6.06 vs 3.71; p<0.0001), and minimal disease activity (19.0 percent vs 10.2 percent; p=0.0012).

In addition, nominally significant differences were met for the following outcomes: FACIT-Fatigue (4.6 vs 2.0; p<0.0001), dactylitis resolution (57.6 percent vs 44.1 percent; p=0.0100), and Disease Activity Score 28-CRP (‒1.33 vs ‒0.83; p<0.0001).

“Deucravacitinib met the primary endpoint of ACR20 at week 16 and showed superiority vs placebo for clinical benefit in musculoskeletal and skin manifestations, as well as patient-reported outcomes,” van der Heijde said.

Prespecified radiographic analysis did not show a statistically significant between-group difference in mean change from baseline in modified Sharp-van der Heijde (mSvdH) score (0.78 vs 0.64; p=0.7597). However, post hoc nonparametric radiographic analysis results in the same population were statistically significant for deucravacitinib vs placebo.

Additionally, analysis of all available radiographic assessments revealed a statistically significant difference between the two groups (mSvdH score with windowing: 0.41 vs 0.50; p=0.0187; without windowing: 0.37 vs 0.60; p=0.0090).

“Although the prespecified analysis of radiographic data did not show a statistically significant difference, post hoc analyses showed evidence of inhibition of radiographic progression in patients treated with deucravacitinib vs placebo at week 16,” van der Heijde said.

Safety

Upper respiratory tract infection was the only adverse event (AE) that occurred in ≥5 percent of patients in either arm (deucravacitinib vs placebo: 5.1 percent vs 3.0 percent) through week 16, while serious AEs (1.8 percent vs 2.4 percent) and discontinuations due to AEs (2.4 percent vs 1.8 percent) were rare.

Moreover, no new safety signals associated with major adverse cardiovascular events, venous or arterial thromboembolic events, malignancies, or opportunistic infections were seen in the deucravacitinib arm.

“Deucravacitinib was well-tolerated,” said van der Heijde, adding that “[t]he safety profile was consistent with that established in the phase II PsA study and the phase III psoriasis clinical program, with no new safety signals.”