Rheumatoid Arthritis (RA)

Background

• Rheumatoid arthritis is a systemic inflammatory disease characterized by symmetric, relapsing, or chronic destructive synovitis. There may also be multisystem involvement.
• The condition is more common in women, with onset between ages 30 and 60 years.
• Rheumatoid arthritis characteristically involves 3 or more proximal interphalangeal (PIP) joints, metacarpophalangeal (MCP) joints, wrist and metatarsophalangeal (MTP) joints, although other joints may be involved as well.
• The eventual, classic presentation is symmetric polyarthritis, but in the early states it can present as oligoarthritis or, less commonly, as recurrent monoarthritis.
• The most common complication is musculoskeletal disability from destructive arthritis.
• Extraarticular complications include rheumatoid nodules, dermal vasculitis, keratoconjuctivitis sicca with associated Sjogren syndrome, interstitial lung disease, pericarditis, mononeuritis multiplex, amyloidosis, and increased cardiovascular mortality, and occur primarily in seropositive patients.

Evaluation

• Consider rheumatoid arthritis in patients with:
  • History of pain and stiffness in multiple joints with initial symptoms predominantly at 1 location or a few scattered sites and fatigue, weight loss, and myalgia.
  • Physical exam findings of boggy, tender, warm joints, puffy hands, atrophy of muscles near affected joints, weakness out of proportion to pain, joints held in flexion, or positive squeeze test.
• The most common presentation is the insidious development of arthralgia, arthritis, malaise, and fatigue over several weeks, however, an acute polyarticular development over a few days is possible.
• Morning stiffness (gelling) usually lasting > 30 minutes is a common feature and is usually relieved with activity and warmth.
• Suggested initial testing in patients suspected to have RA includes rheumatoid factor (RF), anticyclic citrullinated peptide (anti-CCP) antibodies, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complete blood count (CBC) with differential, metabolic panel, and x-rays of significantly involved joints.
• American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA may help guide therapy and predict progression of disease.
• Early rheumatoid arthritis should be distinguished from other conditions that can cause joint pain and inflammation, so that treatment with disease-modifying therapy can be started before erosive joint destruction has begun.

Management

• Disease-modifying antirheumatic drugs (DMARDs) are recommended as first-line therapy and should be started early in the diseases course.
• Prior to starting DMARD therapy:
  • screen for hepatitis B, hepatitis C, and latent tuberculosis infections
  • give all age-/risk-appropriate immunizations
• Patients should be managed with a treat-to-target approach.
  • Clinical remission should be the primary treatment target, but low disease activity may be appropriate for patients with long-standing disease or comorbidities.
  • Consider therapeutic adjustments every 3 months until the treatment target has been reached.
  • Choices of drug adjustments are based on the disease activity and history of failed DMARDs.
  • Consider tapering DMARD therapy when the treatment target has been reached.
• Select initial therapy based on disease activity (as determined by a validated instrument such as the Clinical Disease Activity Index) and presence of markers of poor prognosis.
  • In most patients, begin DMARD therapy with either methotrexate 10-25 mg once weekly or leflunomide 10-20 mg/day orally.
  • Hydroxychloroquine 200-400 mg/day, minocycline 50-200 mg/day, or sulfasalazine 2-3 g/day are lower-toxicity DMARDs which can be used initially for patients with low disease activity.
• Biologic DMARDs such as tumor necrosis factor (TNF) inhibitors, abatacept, tocilizumab, anakinra, and rituximab are generally recommended after failure of nonbiologic DMARDs, especially in patients with high disease activity or poor prognostic features.
• An oral Janus kinase (JAK) inhibitor such as tofacitinib, baricitinib, or upadacitinib may be considered if the treatment with methotrexate or biologic DMARDs fails or these therapies are contraindicated.
• Adjunct medication therapy:
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) orally or topically may help to control symptoms but are not disease modifying.
  • Corticosteroids orally or intra-articularly may be used for symptom control. Early low-dose steroids added to DMARD therapy may be used to reduce joint destruction and increase clinical remission rates.
• Nonpharmacologic patient management includes patient education, exercise, physical and occupational therapies, and cognitive therapies.
• RA may be associated with both articular and nonarticular complications including; joint deformity, cutaneous changes, cardiovascular, pulmonary, renal, ocular, and neurologic disease.
• Earlier diagnosis and development of new therapeutics appears to have ameliorated historically increased mortality in patients with RA.