Decoding Treatment Failure in Rheumatoid Arthritis
The Arthritis Foundation funds researcher’s new work into what causes certain RA patients to be unresponsive to multiple standard treatments.
Por Vandana Suresh, PhD | 10 de marzo de 2026
When two or more biological or synthetic disease-modifying antirheumatic drugs (DMARDs) with different mechanisms of action are ineffective at reducing rheumatoid arthritis (RA) disease activity, patients are in treatment failure. These patients often experience persistent arthritis pain. Therefore, identifying new therapeutic targets for RA patients who are non-responsive, or “refractory,” to conventional immunosuppressive therapies is an active area of study.
Supporting research in RA development and progression, the Arthritis Foundation has awarded a RA Research Award to Kevin Wei, MD, PhD, assistant professor of medicine at Brigham and Women’s Hospital. With the Foundation’s funding, Dr. Wei and his team will investigate the mechanisms that lead to treatment failure in difficult-to-treat RA and provide a rationale for the development of novel treatment strategies for this type of RA.
“Patients with difficult-to-treat RA often end up being on some combination of these drugs, including perhaps, prednisone, which is bad for their body, particularly, the bones, and yet they're probably in pain,” says Dr. Wei. “I would argue that our field right now recognizes that understanding and finding treatment for difficult-to-treat RA as one of the biggest unmet needs.”
To gain more insight into the molecular and cellular mechanisms that underlie refractory RA, researchers have been searching for cellular culprits in the synovium, the lining of the joint. Investigators have found that synovial tissue from patients receiving immunosuppressive treatment for refractory RA have relatively few immune cells, as expected. However, these patients’ synovium had scarring or fibrotic tissue, particularly near blood vessels. This observation is an important clue for Dr. Wei.
“Fibroblasts are not an exclusive joint tissue, their job is like a glue, to hold the tissue together, and if you have an injury, their job is to help you heal,” says Dr. Wei. “But the problem here is that in the joints of refractory RA patients, they cause scarring, which was very interesting and an open question.”
Using a novel method to map gene expression in synovial tissue biopsies, Dr. Wei and his team discovered a biochemical pathway that instructs joint fibroblasts to produce neurotrophins (link opens in new tab), a family of proteins that promote nerve growth, in joint fibroblasts. The goal of the Arthritis Foundation-funded project is to define the link between neurotrophins, blood vessels and nerve growth in joints of refractory RA patients. The long-term goal of the project is to determine if targeting neurotrophins, for which FDA-approved drugs already exist, is a manageable therapy for refractory RA.
“Without the Foundation, it would not be possible to conduct this very disease-specific research,” says Dr. Wei. “Especially in the current funding environment where there's a lot of federal funding uncertainty, having the Foundation to really support patient-centered research is invigorating.”
When two or more biological or synthetic disease-modifying antirheumatic drugs (DMARDs) with different mechanisms of action are ineffective at reducing rheumatoid arthritis (RA) disease activity, patients are in treatment failure. These patients often experience persistent arthritis pain. Therefore, identifying new therapeutic targets for RA patients who are non-responsive, or “refractory,” to conventional immunosuppressive therapies is an active area of study.
Supporting research in RA development and progression, the Arthritis Foundation has awarded a RA Research Award to Kevin Wei, MD, PhD, assistant professor of medicine at Brigham and Women’s Hospital. With the Foundation’s funding, Dr. Wei and his team will investigate the mechanisms that lead to treatment failure in difficult-to-treat RA and provide a rationale for the development of novel treatment strategies for this type of RA. “Patients with difficult-to-treat RA often end up being on some combination of these drugs, including perhaps, prednisone, which is bad for their body, particularly, the bones, and yet they're probably in pain,” says Dr. Wei. “I would argue that our field right now recognizes that understanding and finding treatment for difficult-to-treat RA as one of the biggest unmet needs.”
To gain more insight into the molecular and cellular mechanisms that underlie refractory RA, researchers have been searching for cellular culprits in the synovium, the lining of the joint. Investigators have found that synovial tissue from patients receiving immunosuppressive treatment for refractory RA have relatively few immune cells, as expected. However, these patients’ synovium had scarring or fibrotic tissue, particularly near blood vessels. This observation is an important clue for Dr. Wei.
“Fibroblasts are not an exclusive joint tissue, their job is like a glue, to hold the tissue together, and if you have an injury, their job is to help you heal,” says Dr. Wei. “But the problem here is that in the joints of refractory RA patients, they cause scarring, which was very interesting and an open question.”
Using a novel method to map gene expression in synovial tissue biopsies, Dr. Wei and his team discovered a biochemical pathway that instructs joint fibroblasts to produce neurotrophins (link opens in new tab), a family of proteins that promote nerve growth, in joint fibroblasts. The goal of the Arthritis Foundation-funded project is to define the link between neurotrophins, blood vessels and nerve growth in joints of refractory RA patients. The long-term goal of the project is to determine if targeting neurotrophins, for which FDA-approved drugs already exist, is a manageable therapy for refractory RA.
“Without the Foundation, it would not be possible to conduct this very disease-specific research,” says Dr. Wei. “Especially in the current funding environment where there's a lot of federal funding uncertainty, having the Foundation to really support patient-centered research is invigorating.”
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