Insights into the treatment of rheumatoid arthritis: A paradigm in medicine.

Insights into rheumatoid arthritis (RA) have slowly evolved over the last century, but with breathtaking speed over the last 2 decades. While only aspirin and parenteral gold were available in early 20th century, the efficacy of sulfasalazine, glucocorticoids and methotrexate was established around its middle. Identification of pathogenetic pathways was slow, and until today the role of T-cells is enigmatic, while it is clear that genetics via the shared epitope and other genes as well as environmental factors including the metagenome play major roles. More clarity evolved on importance of proinflammatory cytokines, especially TNF and IL-6. The activation of osteoclasts, the culprits of bony joint damage, is amplified by the proinflammatory cytokines. The realization of TNF's central role led to the successful introduction of TNF-inhibitors and subsequently also inhibitors of other cytokines and cells as well as signal transduction. In parallel, the evolution of outcomes research has contributed importantly to RA management. At the turn to the 21st century, improvement criteria and continuous indices were created, allowing reliable therapeutic response determination, including definition of endpoints like remission. Also our understanding of the role of disease activity relative to disease pathology has increased, ultimately fostering the treat-to-target concept and recommendations and, thus, optimal outcomes for RA patients as never been seen before. Similar developments are now ultimately being introduced in the field of psoriatic arthritis. Here many of these aspects are reviewed from a very personal perspective of the author in the hopes of further helping parients with chronic forms of arthritis.