Rheumatoid Arthritis Medications Quiz

Rheumatoid Arthritis Treatment

• Rheumatoid arthritis (RA) is a debilitating autoimmune disease
• The initial impact of RA causes significant disability
• The goal is to control RA early to minimize long-term effects
• Treatment involves: patient education, healthcare professional management, medication, and surgery

Drugs for RA

• Anti-inflammatory drugs: These have little effect on disease progression
  • Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • COX-2 inhibitors
  • Glucocorticoids (e.g., prednisolone)
• Disease-Modifying Anti-Rheumatic Drugs (DMARDs): Compounds that may limit disease progression
  • Conventional DMARDs (cDMARDs)
  • Biologics

Glucocorticoids (e.g., Prednisolone)

• Useful "bridging" drug
• Administered orally, intramuscularly, or intra-articularly
• Actions: anti-inflammatory and immune suppression
  • Inhibit cytokine gene expression (IL-1, IL-2, IL-6, TNFα)
  • Inhibit inflammatory cell action (decreasing T cell activity and proliferation)

Side Effects of Glucocorticoids (Cushing Syndrome)

• Euphoria (though sometimes depression or psychosis)
• Emotional lability
• Buffalo hump
• Hypertension
• Moon face (plethoric cheeks)
• Increased abdominal fat
• Avascular necrosis of femoral head
• Easy bruising
• Thinning skin
• Thin arms and legs, muscle wasting
• Poor wound healing
• Osteoporosis
• Tendency to hyperglycemia
• Negative nitrogen balance
• Increased appetite
• Increased susceptibility to infection
• Obesity

Steroid Formulations (e.g., Lodotra)

• Prednisone modified-release formulation
• Activated approximately 6 hours post-ingestion
• Taken with water, after food; do not chew
• Released to coincide with circadian rhythms of cortisol & disease symptoms (peak early morning)
• Studies show improvement in early morning joint stiffness symptoms

DMARDs (Disease-Modifying Anti-Rheumatic Drugs)

• Conventional DMARDs (e.g., methotrexate, azathioprine, cyclosporin, leflunomide, sulfasalazine, sodium aurothiomalate, penicillamine, hydroxychloroquine sulfate)
• Biologic DMARDs
• Effective in limiting disease progression
• 90% of RA joint involvement occurs within the first year; early aggressive treatment is crucial.

DMARDS Effects

• Shown to reduce swelling, pain, and improve joint function

cDMARDs (Conventional DMARDs)

• Methotrexate
• Azathioprine
• Cyclosporin
• Leflunomide
• Sulfasalazine
• Sodium aurothiomalate
• Penicillamine
• Hydroxychloroquine sulfate

Immunosuppressants

• Induce and maintain remission, but impair immune response (i.e., increasing susceptibility to infection)
• Methotrexate and leflunomide are commonly used .
• Azathioprine and ciclosporin are less frequently used due to better alternatives

Methotrexate

• Folic acid antagonist and inhibitor of dihydrofolate reductase. Inhibits DNA synthesis
• Also interferes with IL-1 proinflammatory actions
• Also promotes adenosine release (anti-inflammatory)
• Side effects: myelosuppression, mucositis, GI disorders, hepatotoxicity, pneumonitis, teratogenic
• Co-administration of folic acid supplements reduces myelosuppression and mucositis

Leflunomide

• Prodrug converted to teriflunomide in the body
• Inhibits pyrimidine synthesis (blocking dihydroorotate dehydrogenase)
• Targets rapidly dividing cells (T-cells)
• Used for moderate to severe rheumatoid arthritis
• Side effects: GI disturbances, peripheral neuropathy, risk of hepatic failure
• Long half-life

Sulfasalazine

• Broken down by gut bacteria (azoreductase) to 5-aminosalicylate (5-ASA) and sulfapyridine
• Absorbed into systemic circulation
• Acts in the lumen to have anti-inflammatory effects
• Therapeutic use through inhibition of PGs and LTs, and pro-inflammatory cytokines (IL-1, TNFα)
• Side effects: GI disturbances, malaise, headache, severe adverse reactions (including reduced WBC counts, caused by sulfapyridine)

Hydroxychloroquine sulfate

• Weak DMARD with a slow onset of action
• Prevents antigen processing by immune cells, preventing immune response
• Effective against autoimmune responses
• Use in mild RA, with methotrexate and sulfasalazine (triple therapy)
• Potential serious side effects (especially with overdose), including cardiovascular and psychiatric effects

Biological DMARDs

• Many treatment options (see Canvas)
• Recommended when conventional therapies are ineffective
• Target numerous pathways in RA, specifically TNF alpha, other cytokines (e.g., IL-6), and other targets
• Examples include: Etanercept, Infliximab, Anakinra, Abatacept, Tocilizumab, Sarilumab, Rituximab

International Non-Proprietary Names (INNs) for Antibodies

• Provides common names for antibodies used in RA treatment across different origins (Chimeric, Humanised, Human) e.g., Infliximab, Tocilizumab, Sarilumab

Immunogenicity

• Different antibody origins (murine, chimeric, humanized, human) exhibit varying levels of immunogenicity (i.e., a reduced reaction from the body)

Biological Therapy for RA

• Includes drugs such as Etanercept, Infliximab, Anakinra, Abatacept, Tocilizumab, Sarilumab, Rituximab
• Used in conjunction with methotrexate (MTX)
• Targeting TNF, IL-1, IL-6 receptor, and other targets

Treatment Flowchart NICE

• Mono-therapy with cDMARDs (MTX, Leflu, Sulfasalazine, Hydroxychloroquine) for mild cases
• MTX with Biological therapies (TNFalpha inhibitors)
• Other biological drugs (e.g., Rituximab) with or without MTX
• Other biological drugs (e.g., Sarilumab, tocilizumab) with or without MTX

Other Compounds

• Synthetic DMARDs (e.g., tofacitinib, baricitinib, upadacitinib)
• Janus kinase (JAK) inhibitors
• Used under expert supervision
• Risks include: cardiovascular events, venous thromboembolism, malignancies, serious infections, and increased mortality

Rheumatoid Arthritis vs. Osteoarthritis

• Differentiated based on features like joint involvement patterns (symmetrical/asymmetrical), presence of nodules, and morning stiffness duration, cartilage loss, inflamed synovium
• RA is autoimmune, while osteoarthritis is degenerative

Key Differences between RA and OA

These are summarized in a table

Self-Assessment Questions

• Questions about RA diagnosis, pathogenesis-implicated cytokines, differences between anti-inflammatory and immunosuppressant drugs, and biological drugs used for treatment.