Phase 3 data presented at ACR Convergence 2025 highlight distinct biological pathways in male and female patients, yet a shared response to TYK2 inhibition.
A pooled phase 3 analysis has provided new insight into sex-specific proteomic differences in patients with active psoriatic arthritis and how these differences respond to treatment with deucravacitinib, a selective tyrosine kinase 2 (TYK2) inhibitor.
University of Toronto Associate Professor of Medicine Dr Lihi Eder and colleagues presented their research at ACR Convergence 2025 on Monday.
The post hoc analysis combined data from two pivotal, randomised, placebo-controlled studies known as POETYK PsA-1 and POETYK PsA-2, and explored biological pathways underlying disease manifestations in male and female patients.
Proteomic profiling was conducted on plasma samples from more than 1200 patients with PsA and 121 healthy volunteers using the Olink 3072 platform, which measures approximately 3000 proteins.
Differential expression analyses revealed substantial deviations in protein expression between PsA patients and healthy controls, with key inflammatory mediators such as IL-17, IL-19, beta-defensin and MMP3 upregulated in patients.
Treatment with deucravacitinib led to a reduction in these elevated proteins compared with placebo, aligning with clinical improvements observed in prior trials.
Sex-based comparisons identified distinct proteomic signatures, the researchers found.
Female patients exhibited greater enrichment in pathways related to neuroactive ligand receptor interaction and hormone metabolism, while males showed differing profiles of immune-related proteins.
Despite these baseline differences, deucravacitinib consistently reduced disease-related proteomic signature scores in both sexes by week 16, indicating broad anti-inflammatory and disease-modifying effects across biological variations.
“Deucravacitinib reduced upregulated proteins in all patients,” the researchers concluded.
“Unique proteomic profiles were identified in male vs female patients with PsA.
“Deucravacitinib reduced disease state signature scores in the overall population, male patients, and female patients, which is consistent with improved clinical efficacy in the overall population and by sex.
“Deucravacitinib also reduced disease activity signature scores in male and female patients. Findings provide insight into sex-specific PsA disease biology and may help personalise disease management.”
This wasn’t the only session to discuss deucravacitinib and the POETYK trials.
Bristol Myers Squibb, which markets the TYK2 inhibitor under the brand name Sotyktu, also announced new late-breaking results highlighting the efficacy and safety of deucravacitinib in PsA and systemic lupus erythematosus (SLE).
The data, presented at the ACR, strengthens the evidence supporting deucravacitinib as a potential new oral treatment option across multiple rheumatic diseases.
Week 52 results from the pivotal phase 3 POETYK PsA-1 trial demonstrated that deucravacitinib achieved and sustained meaningful clinical responses in adults with active psoriatic arthritis who were biologic DMARD-naïve.
The trial met its primary and key secondary endpoints, showing significant improvements in American College of Rheumatology (ACR) 20 responses at Week 16 (54.2% vs. 34.1% with placebo, p<0.0001), which continued to improve through Week 52 (63.1%).
Related
Patients who switched from placebo to deucravacitinib at Week 16 achieved similar responses by Week 52 (60.8%). The safety profile remained consistent with prior data and no new safety signals were observed, the researchers found.
Radiographic analyses confirmed sustained inhibition of structural joint damage, with a greater proportion of patients on deucravacitinib showing no progression at Week 52 compared with those initially on placebo.
Patients also experienced improvements across joint and skin manifestations, patient-reported outcomes, and extra-articular symptoms, with continued gains beyond Week 16. The most common adverse event was upper respiratory infection, and rates of serious adverse events and discontinuations were low.
“Psoriatic arthritis is a heterogeneous disease that affects patients in diverse and often debilitating ways, and there remains a clear need for oral therapies that can address both joint and skin symptoms,” said Dr Philip Mease, director of rheumatology research at Providence Swedish Medical Centre and clinical professor at the University of Washington School of Medicine, Seattle in a statement.
“These compelling results build on the previously disclosed data, showing that Sotyktu delivered meaningful improvements across key domains of psoriatic arthritis disease activity with a consistent safety profile, supporting the potential for Sotyktu as a new, first-line, advanced, oral option for patients living with psoriatic arthritis.”
In parallel, integrated data from the Phase 2 PAISLEY-SLE and long-term extension studies confirmed the sustained efficacy and safety of Sotyktu for up to four years in patients with moderate-to-severe systemic lupus erythematosus.
The analyses showed durable responses across standard lupus outcome measures, including the SLE Responder Index-4, BICLA, Lupus Low Disease Activity State and CLASI-50, with no new safety concerns identified over long-term follow-up.
“New systemic treatments for lupus are urgently needed since as many as half of patients do not attain treatment goals in response to current treatment options and no new oral therapy has been approved in decades,” said Professor Eric Morand, head of Rheumatology at Monash University in Melbourne in a statement.
“These results are important for physicians, as they represent the longest follow-up of a TYK2 inhibitor in systemic lupus erythematosus to date, supporting this approach as a novel oral therapy with the potential to maintain both efficacy and a favourable safety profile over extended periods of time.”
In the PAISLEY-SLE studies, serious adverse events occurred in 17.0%, 14.9%, and 21.8% of patients receiving deucravacitinib 3mg twice daily, 6mg twice daily and 12mg once daily, respectively.
Discontinuations due to adverse events were reported in 13.4%, 11.4% and 17.3% of patients across these groups. Patients who transitioned from placebo to deucravacitinib in the long-term extension achieved comparable clinical responses to those on continuous treatment.
Dennis Grasela, vice president and senior global program lead for Immunology and Cardiovascular at Bristol Myers Squibb, said the findings reinforced the company’s confidence in deucravacitinib’s potential across immune-mediated diseases.
“These data underscore our commitment to advancing innovative therapies that address unmet needs in rheumatology,” he said.
“We look forward to ongoing regulatory discussions to expand Sotyktu’s label for psoriatic arthritis and to progressing our Phase 3 lupus program.”
In addition to the deucravacitinib presentations, Bristol Myers Squibb also presented data at ACR Convergence 2025 from its broader lupus program, including early-phase studies of its CD19-targeted CAR T cell therapy (BMS-986353) in severe, refractory SLE, systemic sclerosis and idiopathic inflammatory myopathies.
ACR Convergence 2025 was held in Chicago from 24-29 October.
