Mass General Brigham researchers identify scar-driven cause of persistent rheumatoid arthritis
Updated
Updated · SciTechDaily · May 3
Mass General Brigham researchers identify scar-driven cause of persistent rheumatoid arthritis
8 articles · Updated · SciTechDaily · May 3
In a Nature Immunology study, Kevin Wei and Kartik Bhamidipati found fibroblasts, TGFβ signalling and disrupted vessel-cell communication linked to ongoing pain despite reduced swelling.
Using high-resolution spatial transcriptomics, the team showed exaggerated wound-healing and joint scarring persist in some patients even after immune-targeting treatments deplete inflammatory cells.
The findings could open new targeted therapies for treatment-refractory RA, which affects an estimated 6% to 28% of patients who fail to reach remission after multiple treatments.
Could targeting joint scarring finally offer relief for rheumatoid arthritis patients who don’t respond to current anti-inflammatory treatments?
How soon might new antifibrotic therapies or advanced diagnostic tools reach patients with treatment-resistant rheumatoid arthritis?
Targeting Fibrosis in Rheumatoid Arthritis: New Insights into COMP-High Fibroblasts and Anti-Fibrotic Therapies
Overview
A landmark 2026 study revealed that treatment-resistant rheumatoid arthritis (RA) is driven by fibrosis caused by COMP-high fibroblasts activated through disrupted Notch and TGFβ signaling. These fibroblasts produce excessive collagen, leading to irreversible joint damage, and are not targeted by current anti-inflammatory therapies, which often allow their expansion. This discovery has spurred the development of new anti-fibrotic drugs like SOF10 and nerandomilast, with combination therapy proposed to address both inflammation and fibrosis. Advances in blood-based biomarkers and multi-omics approaches aim to identify fibrotic RA patients early, while shared mechanisms with lung fibrosis highlight the need for multidisciplinary care and precision medicine.