Blood-Based Test May Predict Response Across Rheumatoid Arthritis Drug Classes

The lack of a test to guide treatment decisions can lead to variations in clinical practice. A blood-based biomarker test under development aims to address this gap by helping clinicians select targeted therapies before initiating or changing treatment.

Aqtual’s (Hayward, CA, USA) rheumatoid arthritis treatment selection test is designed to help physicians choose among TNF inhibitors, JAK inhibitors, and abatacept. The test uses active chromatin cell-free DNA (cfDNA) technology to detect biological signals in blood, analyzing protein regulation, epigenetics, and transcriptomics through circulating cfDNA fragments.

The findings were presented in two posters at the American College of Rheumatology Convergence 2026 in Orlando, Florida. Both drew on PRIMA-102, a prospective, multicenter study involving more than 1,400 adults with rheumatoid arthritis across more than 50 sites in 22 states. In an interim analysis of baseline plasma samples from 416 participants, researchers profiled active chromatin cfDNA across approximately 37,000 gene promoters to identify drug-class-specific regulatory signatures associated with treatment response at 12 weeks.

Treatment response was defined as achieving a minimal clinically important difference in the Clinical Disease Activity Index. Responders showed distinct biological signatures associated with immune activity for TNF inhibitors, cytokine signaling for JAK inhibitors, and adaptive immune regulation for abatacept. Nonresponse was linked to stromal, myeloid, and fibroblast-related pathways. These signatures also showed strong concordance with previously published synovial tissue pathotypes.

The second poster assessed how well PRIMA-102 participants represented patients receiving routine rheumatoid arthritis care at the same practices. Of 1,131 participants across 20 sites, 580 (51.3%) were linked to at least one real-world data source through privacy-preserving matching. Match accuracy was high, with 99.0% of electronic health record matches identified as unique one-to-one matches and 95.6% of claims matches confirmed by a rheumatoid arthritis diagnosis.

“In our recent 2026 Arthritis Care & Research study of more than 37,000 newly diagnosed RA patients, TNF inhibitors, JAK inhibitors, and abatacept accounted for most first- and second-line advanced therapy choices, TNF inhibitor cycling remained common, and switching rates varied more than four-fold between rheumatologists. That variation in part reflects the absence of a test to guide treatment switching. A blood test that accurately predicts response across RA drug classes would greatly inform the decisions that rheumatologists make most often,” said Jeffrey R. Curtis, MD, MS, MPH, Professor of Medicine at the University of Alabama at Birmingham.

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