Advances in The Management of Rheumatic Disease - Episode 5
Sergio Schwartzman, MD: The therapeutic landscape for the management of the inflammatory arthritides has evolved dramatically. Three to 4 decades ago, all we had available were nonsteroidal anti-inflammatory agents, gold [sodium aurothiomalate], and penicillin. That was the extent of the therapies that we had available to manage patients with rheumatoid arthritis, psoriatic arthritis, and back then ankylosing spondylitis.
A huge breakthrough occurred in the 1980s, when methotrexate was added to our therapeutic landscape as a critical element in the management of 2 out of the 3 of these diseases. It’s not very helpful for axial spondyloarthritis or ankylosing spondylitis. But nonetheless, it introduced the concept of suppressing the immune system, albeit not in a very specific way, as a therapeutic strategy for managing patients with inflammatory arthritides.
In 1998, 2 drugs were approved that were the first 2 biologics—infliximab and etanercept. That really turned the world of management of patients with inflammatory arthritis upside down. This is because for the first time we had targeted therapies that focused on a single cytokine that was overexpressed back then in patients with rheumatoid arthritis. This anti-TNF [tumor necrosis factor] class has grown to the point that we now have 5 anti-TNF therapies. They’re all slightly different both in structure, sometimes in indications as well.
Once this strategy took hold, we also recognized that there are other cytokines that are overexpressed in patients with inflammatory arthritides. With regard to these, interleukin-6 is overexpressed, and we have 2 therapies that target interleukin-6. Interleukin-17 is overexpressed, and this is more in the spondyloarthritides—psoriatic arthritis, ankylosing spondylitis, and nonradiographic axial spondyloarthritis as well.
Interleuken-1 is overexpressed in rheumatoid arthritis and in adult-onset Still disease as well. We have a number of therapies that target interleukin-1. We have 2 other biologic classes that really take advantage of cell interactions, and that’s abatacept, which is the costimulatory molecule blocker, and rituximab is a therapy that actually kills a cell that we think is critical in patients with some rheumatic disease.
For some of our disease states, such as rheumatoid arthritis, we know that antibody production is a critical element. By killing these cells, you obviate not only the antibody production but the other functions of the cell type. We have had the DMARDS [disease-modifying antirheumatic drugs], and I mentioned methotrexate before. I would add leflunomide, sulfasalazine, hydroxychloroquine. We have the biologic classes, which target different cytokines or cell processes. The newest class is the targeted synthetics. Although targeted synthetics will live for a long time with biologics, I would argue that over time it will replace them.
We now have 3 targeted synthetics, or what used to be called small molecules, that are available for the management of rheumatic diseases. We have 1 PDE4 inhibitor, we have 2 JAK inhibitors, with a third literally around the corner, and yet another that will be approved in 4 years.
Transcript edited for clarity.