DMARDs in Rheumatoid Arthritis
Introduction: Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disorder predominantly involving synovial joints, characterized by persistent synovitis, systemic inflammation, and autoantibody production. Untreated or inadequately treated RA leads to joint destruction, deformity, loss of function, and increased morbidity. Disease-modifying antirheumatic drugs (DMARDs) form the foundation of RA management by targeting the underlying immunopathology, reducing inflammation, preventing joint damage, and improving long-term outcomes. This comprehensive discussion covers the pathophysiological rationale, classification, clinical application, detailed pharmacology, monitoring, complications, and therapeutic algorithms of DMARDs, tailored for postgraduate orthopaedic candidates.
1. Pathophysiological Rationale for DMARD Use in RA
RA pathogenesis is complex involving genetic predisposition (e.g., HLA-DRB1 shared epitope), environmental triggers (smoking, infections), and aberrant immune responses targeting synovium. The key pathophysiologic events include:
- Autoimmunity: Production of autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) directed against citrullinated peptides.
- Chronic Synovitis: Infiltration of synovium by T cells, B cells, macrophages, and plasma cells.
- Cytokine Cascade: Pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6) stimulate synoviocyte proliferation and pannus formation, promoting joint destruction.
- Tissue Destruction: Activation of osteoclasts and matrix metalloproteinases leads to cartilage degradation and bone erosion.
Conventional anti-inflammatory drugs (non-steroidal…