First-in-class oral TYK2 inhibitor shows rapid efficacy in PsA

Deucravacitinib, a first-in-class oral TYK2 inhibitor, demonstrated clinical benefits in psoriatic arthritis (PsA) over placebo at 16 weeks, with rapid clinical response, favourable safety profile, and signs of radiographic progression inhibition.

Deucravacitinib is an allosteric, selective TYK2 inhibitor, already approved for plaque psoriasis and is now being investigated in the phase 3 POETYK PsA-1 study (NCT04908202) in biologic-naïve PsA patients at high risk of radiographic progression. Prof. Désirée van der Heijde (Leiden University Medical Center, the Netherlands) presented the 16-week data of this randomised, placebo-controlled trial in a late-breaking abstract session [1].

A total of 670 participants with active PsA and at least 1 radiographic erosion were randomised to receive either deucravacitinib 6 mg once daily (n=336) or placebo (n=334).

Regarding the baseline clinical characteristics, Prof. van der Heijde pointed out a slight imbalance in the radiographic score, with more damage in the placebo group.

At week 16, deucravacitinib achieved the primary endpoint, with 54.2% of participants reaching an ACR20 response versus 34.1% in the placebo group (P<0.0001). Similarly, ACR50 and ACR70 rates were higher with deucravacitinib. These benefits were consistent regardless of baseline high-sensitivity CRP levels or concomitant DMARD use.

Secondary endpoints, including functional capacity and skin clearance, also significantly favoured deucravacitinib. In the SF-36 Physical Component Summary, patients on deucravacitinib experienced significantly greater gains than placebo (6.06 vs 3.71; P<0.001).  Nominal improvements were observed in fatigue (assessed by FACIT), dactylitis resolution, and DAS28-CRP.

Although the prespecified week 16 analysis of radiographic progression did not reach statistical significance, 2 post hoc analyses (based on observed data) revealed significant inhibition of radiographic progression compared with placebo. In the prespecified population, 82% of deucravacitinib-treated participants had no radiographic progression (change ≤0) versus 72.9% on placebo (P=0.02). In the full population, this was 82% versus 71.5% (P=0.003).

Safety findings through 16 weeks were consistent with the known profile of deucravacitinib. Upper respiratory tract infection was the most common adverse event (5.1% with deucravacitinib vs 3.0% with placebo). Serious adverse events and discontinuation rates were low and balanced.

These results confirm the efficacy of TYK2 inhibition in PsA and support deucravacitinib as a new potential oral treatment option in patients with active PSA.

1. Van der Heijde D. Efficacy and safety of deucravacitinib up to week 16 from POETYK PsA-1: a multicenter, randomized, double-blind, placebo-controlled, phase 3 study in patients with active psoriatic arthritis. LB0001, EULAR 2025, 11–14 June, Barcelona, Spain.

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Posted on 18 June 20258 August 2025