Arthritis, Rheumatoid

Importance Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and destruction of cartilage and adjacent bone and can lead to irreversible disability. Rheumatoid arthritis affects 0.53% of adults worldwide and 0.74% of US adults.

Observations Rheumatoid arthritis is more common among females than males (2:1) and has a peak incidence at ages 55 to 75 years. Rheumatoid arthritis can affect all synovial joints, and extra-articular involvement may include rheumatoid nodules, vasculitis, and rheumatoid lung disease. At diagnosis, approximately 40% to 60% of patients have autoantibodies (eg, rheumatoid factor and/or anticitrullinated peptide antibodies). There are no formal diagnostic criteria for RA, so the diagnosis is based on clinical history, characteristic joint swelling in proximal interphalangeal, metacarpophalangeal, and/or wrist joints and often presence of autoantibodies and elevated C-reactive protein levels. Early diagnosis, ideally within 6 weeks of symptom onset, allows rapid initiation of therapy with disease-modifying antirheumatic drugs (DMARDs), which inhibit inflammation and decrease the risk of joint destruction. The goal of treatment is to achieve at least 50% improvement in disease activity by 3 months and remission or low disease activity at 6 months, measured by validated indexes such as the Clinical Disease Activity Index (CDAI). The European Alliance of Associations for Rheumatology recommends starting treatment with methotrexate, 7.5 mg to 10 mg orally weekly, increasing to 20 mg to 25 mg weekly within 4 to 8 weeks, and considering addition of short-term glucocorticoids (eg, prednisone, 5-7.5 mg/d), tapered and discontinued within 3 months, or 1 intramuscular injection of 80 mg to 160 mg depot methylprednisolone. For patients with contraindications to methotrexate, sulfasalazine (2-4 g/d) or leflunomide (20 mg/d) is recommended. With treatment, about 40% of patients with newly diagnosed RA achieve CDAI remission within 6 months. Patients who do not achieve remission with first-line DMARDs should be prescribed biological DMARDs (eg, tumor necrosis factor α inhibitors, costimulation inhibitors, interleukin 6 receptor inhibitors, anti-CD20–targeting B cells), or Janus kinase (JAK) inhibitors (in patients not at high risk of thromboembolism, cardiovascular disease, or malignancy). With addition of biological DMARDs or JAK inhibitors to first-line DMARDs, overall remission or low disease activity rates increase to approximately 80%.

Conclusions and Relevance Rheumatoid arthritis is a chronic autoimmune disease that causes joint destruction. First-line initial therapy is methotrexate, with consideration of glucocorticoids as additive therapy. For patients who do not achieve remission with this initial treatment, adding biological DMARDs or JAK inhibitors increases overall remission or low disease activity rates to 80%.