Rheumatoid Arthritis Overview

Rheumatoid Arthritis

• Rheumatoid arthritis (RA) is a chronic, autoimmune inflammatory disorder that affects more than just joints.
• It can damage various body systems, including skin, eyes, lungs, heart, and blood vessels.
• RA occurs when the immune system attacks the body's tissues.
• It causes painful joint inflammation, potentially leading to bone erosion and joint deformity.
• Inflammation can damage other parts of the body.
• RA often starts with smaller joints, eventually spreading to wrists, knees, ankles, elbows, hips, and shoulders.
• Symptoms are usually symmetrical.
• Approximately 40% experience non-joint symptoms.
• RA can affect numerous non-joint structures.
• Treatment aims to lessen pain, inflammation, and joint stiffness; minimize systemic symptoms; and slow disease progression.
• Clinical remission is the primary treatment goal, though low disease activity might suit some patients.

Medications for Rheumatoid Arthritis

• Nonsteroidal anti-inflammatory drugs (NSAIDs): Used for fast symptom relief. Safer than glucocorticoids/DMARDs. Inhibit cyclooxygenase (COX) enzymes.

  • First-generation NSAIDs inhibit COX-1 and COX-2.
  • Second-generation NSAIDs target COX-2 only.
  • Examples include aspirin, ibuprofen, naproxen, diclofenac, meloxicam, and celecoxib (COX-2 inhibitor).

• Black Box Warning for NSAIDs: Increased risk of serious cardiovascular events (MI, stroke), and GI adverse events (bleeding, ulceration, perforation). Risk higher in patients with cardiovascular disease or risk factors.

• Glucocorticoids (Corticosteroids): Powerful anti-inflammatory agents that can relieve symptoms and potentially slow disease progression. Reserved for widespread symptoms, flares, or when starting a DMARD.

  • Long-term use should be a last resort due to numerous risks.
  • Risks: Alter glucose and lipid metabolism, fluid/electrolyte balance; affect numerous bodily systems.
  • Common side effects include: altered metabolism (hyperglycemia, protein wasting, increased lipid deposition), altered immune response (masking infection), impaired bone health (osteoporosis), skin changes, neurological impacts, cardiac issues (hypertension), ocular problems (glaucoma, cataracts), tremors, hunger, agitation, aggression.
  • Chronic use can lead to hypothalamic-pituitary-adrenal axis suppression (HPA axis), Cushing's syndrome, osteoporosis, immunosuppression, and skin changes (atrophy, striae, telangiectasia, acne.)

• Disease-Modifying Antirheumatic Drugs (DMARDs): Drugs that modify the course of RA and can induce remission.

  • Methotrexate (Rheumatrex): Folic acid antagonist that suppresses inflammation and cell replication. Highly effective, but contraindicated during pregnancy and breastfeeding. Risk of bone marrow suppression, renal impairment, hepatotoxicity, secondary malignancy, dermatologic toxicity, secondary infections, severe toxic reactions, embryo-fetal toxicity. Avoid alcohol.
  • Infliximab (Remicade): Monoclonal antibody that binds to TNFα, reducing the body's attack on itself.
  • Leflunomide (Arava): Powerful immunosuppressant. Effective but more hazardous and expensive than methotrexate.
  • Hydroxychloroquine (Plaquenil): Antimalarial drug with a mechanism of action not fully understood in RA. Can cause retinal damage (leading to blindness in rare cases). Prolongs QT interval.

DMARDs (Continued)

• Biologic DMARDs - Tumor Necrosis Factor Inhibitors (TNF-i): These drugs inhibit TNF, but carry similar risks as infliximab.

  • Black Box Warnings for these and other DMARDs include heightened risk of serious infections, severe allergic reactions, and malignancy.

Special Considerations

• Pregnancy and Lactation:
  • Corticosteroids, such as betamethasone and dexamethasone, may be used in pregnancy for preterm labor to stimulate fetal lung maturity. Low doses of systemic corticosteroids might be suitable with breastfeeding. Topical corticosteroids are also safe.
  • Use lowest dose for shortest time possible. Avoid systemic use beyond two weeks.
• Patient Education:
  • Monitor patients carefully, using the lowest effective dose to mitigate side effects.
  • Inform patients about risks and discuss lifestyle modifications.
  • Take corticosteroids with a full glass of water after meals. Keep doses to 20mg or less at a time.
  • Tapering corticosteroids allows adrenal glands to recover normal function to prevent complications.

Tapering Steroids

• Corticosteroid tapering reduces the dose gradually over several days or weeks, depending on the initial dosage, to prevent adrenal insufficiency.

Important additional considerations:

• Short-burst steroid use: While short-bursts (less than 2 weeks) are commonly used, they are not as safe as once thought. During and after short-burst durations, monitor patients closely, for GI bleeding, sepsis and heart failure, especially during the first month. Patient education is critical to minimize risk.
• Prior Medical Testing / immunizations: Before starting DMARDs, screen for Hepatitis B, C, and latent TB. Administer age-appropriate immunizations, prior to starting DMARDs. Live vaccines are contraindicated once treatment begins.
• Medication Interactions: Be aware of potential drug interactions between the mentioned drugs and potentially other medications, particularly methotrexate with alcohol or other liver-metabolized drugs.