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Rheumatoid Arthritis Remittive Agents

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Rheumatoid Arthritis Remittive Agents, Slow Acting Antirheumatics, Rheumatoid Arthritis Disease Modifying Drugs, Disease Modifying Antirheumatic Drug, SAARDs, DMARDs, DMARD

  • Background
  1. Most important agents in Rheumatoid Arthritis
  2. Start early (within 3 months of active disease onset)
  3. Response to these agents is slow over 1-6 months
  4. Combination therapy is optimal (often 3 agents)
  5. Used with NSAIDs or COX2 Inhibitors
  6. Update Vaccines prior to starting DMARDs if possible
    1. Avoid Live Vaccines (e.g. Flumist or Zostavax) while on DMARDs
    2. Influenza Vaccine
    3. Pneumococcal Vaccine
    4. Hepatitis B Vaccine
    5. HPV Vaccine
    6. Herpes Zoster Vaccine
  • Indications
  • Studies suggest starting SAARD early
  1. Randomized trial of n=238 over 1 year follow-up
    1. Less Functional Disability in SAARD and NSAID
    2. Placebo group was NSAID alone
    3. No XRAY differences
    4. Ann Intern Med 124: 699 [PubMed]
  2. Randomized trial of n=102 over 2 years of follow-up
    1. Triple Therapy Combination Management
      1. Methotrexate 7.5 to 17.5 mg each week
      2. Sulfasalazine 500 mg PO bid
      3. Hydroxychloroquine sulfate (Plaquenil) 200 mg bid
    2. Good response (>50% improvement)
      1. Patients on triple therapy: 77% response
      2. Patients on 1 to 2 drugs: 33-40% response
      3. As effective as Methotrexate with biologic DMARD (Monoclonal Antibody or TNF agents)
    3. Drug toxicity
      1. Medications discontinued in 10% patients on 3 drugs
    4. References
      1. O'Dell JR (1996) N Engl J Med 334:1287-91 [PubMed]
  • Protocol
  • Choice of intial agent
  1. Mild disease: Sulfasalazine, Plaquenil or Minocin
  2. Moderate disease: Methotrexate +/- Sulfasalazine
  • Agents
  • First line in moderate to severe disease
  1. Methotrexate
    1. Dosing
      1. Start: Methotrexate 10-15 mg orally once weekly
      2. Advance as needed to 20 mg orally once weekly
      3. Coadminister with Folic Acid 1 mg orally daily (or 5-7 mg once weekly) to reduce side effects
      4. Methotrexate SQ/IM is also available if GI side effects limit use (vial or autoinjector)
    2. Efficacy
      1. Most effective single DMARD
      2. Good benefit to risk ratio
    3. Superior effect with Plaquenil or Sulfasalazine
      1. Methotrexate and
      2. Hydroxychloroquine sulfate (Plaquenil) and
      3. Sulfasalazine (may be used in place of Plaquenil)
    4. Combination with Etanercept reverses joint damage
      1. Klareskog (2004) Lancet 363:675-81 [PubMed]
  2. Leflunomide 20 mg daily
    1. Alternative to Methotrexate (at double cost)
  • Agents
  • Second line (First line if mild disease)
  1. Hydroxychloroquine (Plaquenil) 200 mg PO bid
  2. Sulfasalazine (Azulfidine) 500 mg PO bid to tid
  3. Minocycline 100 mg PO bid
    1. Modest effect
    2. May work best early
  • Agents
  • Third Line Agents
  1. Azathioprine (Imuran) 50 to 150 mg PO qd
    1. Slow onset
    2. Reasonably effective
  2. Anti-Tumor Necrosis Factor Medications (see below)
    1. Advantages: Highly effective in refractory cases
    2. Disadvantages: Costs exceed $15,000 per year
    3. Agents
      1. Adalimumab (Humira)
      2. Etanercept (Enbrel)
      3. Infliximab (Remicade)
      4. Tofacitinib (Xeljanz)
  3. Interleukin-1 Receptor Antagonist (Anakinra or Kineret)
  4. Staphylococcal Protein A Column (Prosorba)
    1. Immunomodulatory effect via IgG binding
    2. Expensive: $1000 per column, done weekly
    3. Felson (1999) Arthritis Rheum 42:2153-59 [PubMed]
  1. Indications
    1. Consider for severe symptoms when starting DMARD
    2. Symptoms refractory to above
    3. More cost-effective than NSAID with prophylaxis (PPI)
  2. Preparations
    1. Intra-articular Corticosteroid
    2. Prednisone 10 mg or less PO qd over limited course
      1. See Corticosteroid Associated Osteoporosis
  • Agents
  • Last ditch effort (very serious adverse effects)
  1. D-Penicillamine
  2. Cyclophosphamide (Cytoxan)
    1. Effective for Vasculitis
  • Agents
  • Rarely used due to decreased efficacy
  1. Parenteral Gold (Solganal)
    1. Slow onset
    2. Decreases progression but rarely remits
    3. Rarely used now
  2. Oral Gold (Auranofin)
    1. Rarely used now due to decreased efficacy
  • Monitoring
  1. All agents above need careful monitoring
  2. Lab Tests every 4-8 weeks
    1. Liver Function Tests
    2. Complete Blood Count
    3. Serum chemistry panel (Chem7)
  3. Physical Exam 3-6 times per year