Deucravacitinib and Renal Function: Insights from the PAISLEY Trial Save

At ACR 2025, we have seen exciting momentum surrounding new therapeutics in autoimmune disease particularly TYK2 inhibition. Among these, deucravacitinib continues to stand out. Demonstrating clinical efficacy in psoriatic arthritis, this agent has also shown promising results in systemic lupus erythematosus.

In the phase 2 PAISLEY trial, deucravacitinib met its primary and secondary endpoints, demonstrating efficacy across multiple clinical and patient-reported outcomes. However, the impact on renal function has remained unclear.

Abstract 2694 provides new insights through a post-hoc analysis examining the effect of deucravacitinib on renal dysfunction using circulating plasma biomarkers. Investigators identified proteins associated with high baseline renal BILAG scores and urine protein-to-creatinine ratio (UPCR) and then assessed how these markers changed with deucravacitinib versus placebo.

The analysis revealed that multiple biomarkers linked to immune dysregulation, including those involved in leukocyte activation, cell adhesion, and cytokine signaling, were significantly reduced at week 32 among patients treated with deucravacitinib. Interestingly, several biomarkers previously associated with low GFR in a phase 3 abatacept lupus nephritis study also declined, suggesting potential renal benefit.

While phase 3 trials of deucravacitinib in systemic lupus erythematosus (SLE) are still underway, these findings hint at a broader therapeutic role particularly in mitigating renal inflammation and injury. Future studies will determine whether these biomarker shifts translate into meaningful clinical improvements in lupus nephritis.