During the past decades important breakthroughs have been made in the treatment of rheumatoid arthritis (RA). First, the implementation of low-dose methotrexate and other conventional disease-modifying anti-rheumatic drugs was introduced as an effective treatment. Second, it was recognized that early immunomodu- tory treatment is crucial for controlling the disease and its long-term destructive effects more effectively. Parallel advances in research on the pathogenesis of RA and cytokine biology converged in identifying tumor necrosis factor (TNF) as a key factor in inflammation and matrix...