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In your journey with rheumatoid arthritis (RA), you may have been treated with methotrexate and one or more of the newer medications such as tumor necrosis factor (TNF) inhibitors. These newer agents have revolutionized the therapy of RA, which formerly was a severely disabling disease associated with many complications and a shortened lifespan.

But the past two decades have seen tremendous changes in the treatment of RA, as researchers identified certain cells and molecules in the immune system and the joints that were contributing to the inflammation responsible for the pain and stiffness in your joints. The TNF inhibitors, initially approved more than 30 years ago, greatly improved symptom control and helped prevent the long-term joint damage that formerly was the expected outcome in RA.

These medications, given intravenously or by subcutaneous injection, were followed by additional therapies as the immune system increasingly gave up its secrets and more cellular and molecular inflammatory factors were identified. These included the interleukin (IL)-6 inhibitors and then oral drugs known as Janus kinase, or JAK, inhibitors.

If you have been treated with any of these medications, you also may have experienced persistent symptoms or your symptoms may have returned after a period of improvement. You also may have developed potentially serious infections, because the available treatments not only target the RA-associated inflammatory cells and pathways, but also suppress the immune system overall, which can interfere with the body's ability to ward off pathogens and cancerous changes. The current therapies also have been associated with a wide range of other adverse events including many heart problems.

But researchers have continued to explore the immune system and the inflammatory processes that underlie RA as well as many other diseases, and have found that certain cells in the lining of your joints may actually be better targets to block than TNF, IL-6, or the Janus kinases. Targeting these cells, known as fibroblasts, could be more effective because they are the actual source of inflammatory cells such as IL-6, and could block the inflammation without interfering with the overall immune system responses.

Targeting fibroblasts in RA is an area of intense research today, using highly advanced technologies, but results are still preliminary and only one clinical trial has been done. That study was not successful, but some experts have suggested that the lack of benefit with the treatment could be explained by the fact that patients were also on TNF inhibitors, which could interfere with the fibroblast-blocking antibody.

Future studies may attempt to identify which patients are most likely to respond to specific therapies, minimizing reliance on a trial-and-error approach. The goal will be to achieve remission in the shortest time possible to prevent damage to the joints altogether.

Researchers remain confident that newer and better treatments for RA are coming that will be more effective and safer, leading to better long-term outcomes and quality of life for all patients with RA.

Read previous installments in this series:

What Is Rheumatoid Arthritis?

How Is Rheumatoid Arthritis Diagnosed?

Starting Treatment for Rheumatoid Arthritis

Beyond the First RA Treatments

Special Concerns About COVID

Reproductive Health in RA

How to Cope With Rheumatoid Arthritis

Heart Health in Rheumatoid Arthritis

"Medical Journeys" is a set of clinical resources reviewed by doctors, meant for physicians and other healthcare professionals as well as the patients they serve. Each episode of this 12-part journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.