Rheumatoid Arthritis Pharmacotherapy

Introduction & pathophysiology

• Rheumatoid arthritis (RA) is a chronic, progressive, systemic autoimmune disease marked by symmetrical small-joint synovial inflammation with pannus formation that erodes cartilage and bone; it affects ~1% of the population and shortens life.
• Driven by an autoimmune cascade — immune complexes (IgM rheumatoid factor) activate complement and release cytokines, chiefly TNF-α and IL-1; infiltrating cells secrete lysosomal enzymes (cartilage/bone damage) while prostaglandins cause pain and vasodilatation.
• Pivotal targets — TNF-α (via TNFR1/TNFR2) and IL-6 are the key proinflammatory cytokines; T-cell activation needs signal 1 (TCR–MHC) plus signal 2 costimulation (CD80/86–CD28); many cytokine receptors signal through the intracellular JAK–STAT pathway — each is a validated drug target.
• Goals of therapy — relieve pain/swelling/stiffness, prevent cartilage damage and bony erosions, preserve joint function and prevent deformity — diagnosis supported by RF, anti-CCP, raised ESR/CRP and radiographic erosions.
• Core strategy — add a DMARD as soon as RA is diagnosed — unlike NSAIDs/steroids, DMARDs suppress the rheumatoid process and retard progression; benefit is slow (2 weeks–6 months, hence the older term slow-acting antirheumatic drugs) and ≥2–3 DMARDs may be combined.