Deucravacitinib improved joint, skin, and patient-reported outcomes in biologic-naive psoriatic arthritis, with responses maintained through 52 weeks and no new safety signals.
An oral selective TYK2 inhibitor has delivered sustained improvements across multiple domains of psoriatic arthritis to 52 weeks, phase 3 data shows.
Results from the POETYK PsA-1 trial showed deucravacitinib was superior to placebo for the primary ACR20 endpoint at week 16, with clinical responses increasing further and generally maintained through one year.
Results have been published this month in the Annals of the Rheumatic Diseases.
The randomised, double-blind trial involved 670 adults with active PsA who were naive to biologic DMARDs.
Patients were required to have at least three swollen and three tender joints, elevated high-sensitivity CRP, and at least one radiographically detected PsA-related erosion in the hands or feet.
Participants were randomised to deucravacitinib 6mg once daily or placebo for 16 weeks, after which the placebo group switched to deucravacitinib and both groups continued active treatment to week 52.
At week 16, 54.2% of patients taking deucravacitinib achieved an ACR20 response compared with 34.1% receiving placebo, a 20 percentage-point difference (p<0.001). ACR50 responses were achieved by 24.7% and 13.5% respectively, while ACR70 responses were seen in 11.6% versus 5.4%.
Benefits extended beyond joint responses. Among patients eligible for psoriasis assessment, 51.9% of the deucravacitinib group achieved PASI75 at week 16 compared with 7.1% of the placebo group. Minimal disease activity was achieved by 19.0% versus 10.2%.
Patients taking deucravacitinib also had greater improvements in physical function and health-related quality of life. Mean HAQ-DI scores fell by 0.39 compared with 0.22 with placebo, while the SF-36 physical component score improved by 6.06 points versus 3.71 points.
Improvements were also reported for fatigue and several measures of pain.
Enthesitis produced a more mixed result. Resolution measured using the Leeds Enthesitis Index did not reach statistical significance, although a pooled analysis using the SPARCC enthesitis measure favoured deucravacitinib.
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Dactylitis resolution also favoured active treatment, although these latter results were nominally significant.
By week 52, ACR20 responses were reported in 63.1% of patients who had received deucravacitinib continuously and 60.8% of those who switched from placebo at week 16.
ACR50 rates were 40.5% and 44.0%, respectively, while around one-quarter of both groups achieved ACR70. Minimal disease activity was reported in roughly one-third of patients in each group.
The researchers said patients who switched from placebo at week 16 generally caught up with those treated continuously, with improvements in clinical efficacy measures and patient-reported outcomes sustained to week 52.
The trial also examined whether deucravacitinib could slow structural joint damage, although interpretation of this finding is less straightforward.
The prespecified parametric analysis found no significant difference in radiographic progression between deucravacitinib and placebo at week 16 (p=0.76). However, almost 20% of available radiographs were excluded under the protocol’s imaging-window rules and the radiographic data were not normally distributed.
Subsequent post hoc analyses using non-parametric rank ANCOVA found significantly less radiographic progression with deucravacitinib in both the protocol-defined and full populations. At week 16, 82.0% of deucravacitinib-treated patients were radiographic non-progressors compared with 72.9% of placebo patients in the protocol-defined population and 71.5% in the full population.
The apparent inhibition of structural damage was maintained through week 52, while patients originally assigned to placebo showed attenuated progression after switching to deucravacitinib.
The researchers said the findings suggested TYK2 signalling inhibition could potentially provide a strategy for managing structural damage in PsA, but acknowledged the radiographic result rested on post hoc analyses.
Safety findings through one year were consistent with the drug’s established profile.
During the 16-week placebo-controlled period, adverse events occurred in 60.2% of deucravacitinib-treated patients compared with 48.0% of placebo recipients. Serious adverse events occurred in 1.8% and 2.4% respectively, while 2.4% of the deucravacitinib group and 1.8% of the placebo group discontinued because of adverse events.
Skin events, including acneiform events, and infections were among the adverse events of special interest. No new safety signals involving major adverse cardiovascular events, venous thromboembolism, malignancy, or opportunistic infections emerged, and there were no deaths.
No meaningful mean changes in liver enzymes, creatine kinase, or triglycerides were observed through week 52, and there were no cases of drug-induced liver injury or rhabdomyolysis.
The researchers noted several limitations, including the relatively short 16-week placebo-controlled period for assessing radiographic progression and the trial’s enrichment for patients at higher risk of progression through requirements for existing erosions and elevated hsCRP.
“However, given the large number of sites and the small number of patients at many sites, and that the primary objective of the trial was the overall population-average treatment effect across the intended target population, the analysis approach was aligned to the estimand rather than a site random-effects model,” they wrote
“Additionally, the 16-week placebo-controlled period may have limited the ability to observe radiographic progression in the placebo group with a less sensitive imaging method such as radiography.”
They also highlighted limitations of the prespecified radiographic analysis and the exclusion of almost one-fifth of available radiographs under the strict imaging window.
However, they found deucravacitinib “demonstrated superiority over placebo in multiple key domains of PsA and PROs”.
“Durable improvements were noted in joints, skin, enthesitis, dactylitis, and overall disease activity outcomes, as well as PROs related to pain, fatigue, physical function, and overall quality of life,” the authors concluded.
