Ex vivo JAK and TNF inhibitor-modulated immune signatures guide first-line therapy selection in rheumatoid arthritis

Background

Rheumatoid arthritis (RA) is a heterogeneous autoimmune disease for which selecting the most appropriate first targeted therapy remains challenging. We integrated ex vivo immune-cell functional assays, targeted proteomics, clinical outcomes, and a three-dimensional (3D) synovial model to identify treatment-associated molecular signatures and evaluate their relationship with subsequent response to Janus kinase inhibitors (JAKi) or tumour necrosis factor inhibitors (TNFi).