Early rheumatoid arthritis: pitfalls in diagnosis and review of recent clinical trials

The treatment of rheumatoid arthritis (RA) has changed dramatically in the past decade as advancements in the understanding of the pathobiology of the disease have led to novel therapeutic agents. The recognition that early diagnosis and treatment leads to improvements in morbidity and mortality has altered the therapeutic strategy such that early therapy is now considered the standard of care. This review focuses on the challenges in making the diagnosis of early RA, including a broad differential diagnosis for inflammatory polyarthritis, poor performance of the standard classification criteria, difficulty in clinical assessment of synovitis, absence of absolute laboratory tests, inability of conventional radiography to detect bony changes early, and barriers to rheumatology care. Additionally, the pathogenesis of RA is highlighted, with particular emphasis on cytokine biology as it relates to therapeutic regimens. Relevant clinical trials in early RA are reviewed and discussed, including trials of combination disease-modifying antirheumatic drugs and biological therapy. The role of induction therapy as a novel therapeutic approach is highlighted. The search for predictors of response is reviewed and the external validity of the trials is analysed. Finally, the trials in early RA therapy suggest that swift intervention with combinations of medications is required for patients with severe RA. However, further research is needed to determine which regimen is appropriate for the individual patient with RA.