Rethinking the Role of Pathogenic Drivers in Rheumatoid Arthritis

December 16, 2019
Sheila Kelly, M.D., U.S. Immunology Medical Lead, Bristol Myers Squibb
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heumatologists are all too familiar with the significant impact rheumatoid arthritis (RA), a destructive, immune-mediated disease, can have on patients. In RA, the body’s immune system quite literally attacks its own joints, causing pain, stiffness and swelling in areas such as the hands, wrists and knees. But, more and more, the community’s collective knowledge of pathogenic drivers and the underlying mechanism of disease continues to evolve, offering physicians and patients the opportunity to rethink approaches to RA. Additionally, research is exploring a potential role for pathogenic drivers in treatment selection in RA.

To help spread the word about these recent findings, Bristol Myers Squibb, working with experts in the field, has created an educational initiative for rheumatologists called Rheumatoid Arthritis, Redefined, featuring Guillermo Valenzuela, M.D., a clinical rheumatologist in Plantation, Fla., who dives deeper into the pathogenesis and autoimmune cycle of RA.

Reviewing the Pathogenesis of RA: Who are the Key Players?

Two pathways play a role in RA: B-cell-derived autoantibodies, such as rheumatoid factors (RF) and anti-citrullinated protein autoantibodies (ACPA); and proinflammatory cytokines, including IL-1, IL-6, IL-8, and TNF-α. Production of both drivers is dependent on T-cell activation. While the impact of proinflammatory cytokines in RA is well known, recent research has deepened our understanding of the role of RF and ACPA. Because they can be present years before an RA diagnosis, and may lead to worse outcomes, such as joint damage, these autoantibodies can be important diagnostic and prognostic biomarkers for physicians to understand and consider.

Learn more in Video #1. 

Click on image to view video.

Rethinking the Autoimmune Cycle: What Drives RA Progression?

Once formed, autoantibodies and proinflammatory cytokines become effector molecules that drive destructive autoimmune disease pathology through feedback loops. The eventual activation of downstream effectors may lead to permanent structural damage, such as bone and cartilage erosion, synovitis, pain, and other joint-related abnormalities.

Learn more in Video #2.

Click on image to view video.

Currently, there are RA treatments available that target a variety of important immune players. Understanding RA initiation, progression and prognosis may aid in treatment decision-making.

Education is at the heart of the Rheumatoid Arthritis, Redefined initiative. We look forward to continuing to share research on pathogenic drivers in RA, as this evolving science may provide insight on precision-focused approaches.

More information, including the full-length Dr. Valenzuela video and downloadable resources, is available here.