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Treatment of Rheumatoid Arthritis Then and Now Objectives: 1. 2. 3. Outline the diagnostic criteria for Rheumatoid Arthritis, its systemic manifestation, and the complication of untreated RA. Identify and discuss laboratory tests that aid in the diagnosis of RA. Explain the differences between oral disease modifying anti-rheumatic medications and biologic medications, including medication risks and safety profiles. Pathophysiology Rheumatology Nurse Newsletter Volume2:2 Cytokines Rheumatology Nurse Newsletter Volume 2:2 Summer 2009 Paradigm shift in the treatment of rheumatoid and inflammatory Arthritis THEN… Mary’s Story 31 year old female who presents to the Beals Institute in 1982 with five year history of RA Disability at age 27 First joint replacement surgery at age 29 Mary’s treatments: Tried and Failed • • • • • • 24 aspirin daily Cyclosporin (Neoral) Plaquenil (Hydroxychloroquine) Injectable Gold Methotrexate Azulfidine • • • • • • Enbrel (Etanercept) D-penicillamine Prednisone NSAIDs Plasmaphoresis Arava (Leflunomide) Mary’s Numbers 3 reconstructive hand surgeries last one 2007 1 wrist fusion 2 hip replacements 2 total knee replacements 1 elbow replacement 1 ulnar fracture repair and prosthetic repair > 10 hospitalizations for flares of uncontrolled disease process Rheumatologist Primary Care Physician • Establish Diagnosis of Rheumatoid Arthritis Early • Document Baseline Disease Activity and Damage (Table 1) • Estimate Prognosis (See Text) Initiate Therapy • Patient Education • Start DMARD(s) Within 3 Months (Table 2) • Consider NSAID • Consider Local or Low-Dose Systemic Steroids • Physical Therapy/Occupational Therapy AND NOW… Periodically Assess Disease Activity (Table 3) Inadequate Response (i.e., ongoing active disease after 3 months of maximal therapy) Adequate Response with Decreased Disease Activity Change/Add DMARDs (Tables 2, 4, and 5) MTX Naive MTX Other Mono Rx Combination Rx Suboptimal MTX Response Combination Rx Other Mono Rx Biologics Mono Rx Combination Rx Multiple DMARD Failure Symptomatic And/or Structural Joint Damage Surgery Figure 1. Outline of the management of rheumatoid arthritis. Each step is detailed in the text. Boxes with heavy borders represent major decision points in management. A suboptimum response to methotrexate (MTX) is defined as intolerance, lack of satisfactory efficacy with a dosage of up to 25 mg/week, or a contraindication to the drug. DMARD = disease-modifying antirheumatic drug; NSAID = nonsteroidal antiinflammatory drug; mono Rx = monotherapy; combination Rx = combination therapy. …Now Abigail’s Story 34 year old presents in 2005 with shoulder, wrist and hand pain for 2 months Started on combination therapy using Arava and Enbrel Due to diarrhea and weight loss, changed to Methotrexate and Enbrel Abigail’s Numbers 0 days missed work due to disability 0 hospitalizations, surgeries and joint replacements due to RA 5K - the length of the races she runs regularly Why Is Early Diagnosis and Treatment Imperative? •Rheumatoid arthritis progression is the most rapid in the first two years of disease onset •75% of joint damage will occur within the first five years of disease onset. •Rheumatoid Arthritis is as lethal as lymphoma if left untreated! Diagnostic Criteria for RA >4 of the following must be present Morning stiffness > 1 hour > 3 joints involved Symmetrical swelling; usually in hands, wrists and MTP joints in feet Rotating joint pain Positive Rheumatoid Factor (Note: 20% of patients with RA will not test positive) Positive CCP Erosive joint changes on x-ray RA nodules Complications of Untreated RA Pulmonary fibrosis Disability Deformity ↓ QOL ↑ morbidity and mortality All Slides (c) Current Medicine Clinical Pearl Hepatitis C presents with identical symptomatology and will cause the Rheumatoid Factor to be positive.. Labs Eval: Arthritis SPEP Sed rate CBC CCP RF HLA-B27 CRP Hepatic panel ANA, ENA, DNA Hepatitis panel Vitamin D Treatment: NSAIDs Celebrex Relafen Lodine Arthrotec Feldene Voltaren Mobic Indocin Daypro Colchicine Treatment: DMARDs Methotrexate Arava (Leflunomide) Plaquenil (hydroxychloroquine) Azulfidine (sulfasalazine) Imuran (azathioprine) Minocin (minocycline) Gold (myochrysine) Neoral (cyclosporine) Treatment: Biologic Agents IL-1 antagonist – Kineret: sc daily TNF inhibitor – – – – – Enbrel: sc 1-2 times/week Humira: sc 2 times a month Remicade: IV q 6 to 8 weeks Simponi: sc q month Cimzia: sc q month T-cell inhibitor – Orencia: IV q month B-cell inhibitor – Rituximab: IV load, 2 weeks then PRN Contraindications of Biologic Agents Active Lupus Tuberculosis Active infection Hypogammaglobulinemia Hepatitis B / C CHF III & IV Demyelinating Disorder A Happy Ending? In January 2004 Mary started Humira Continued Methotrexate, Gold, and episodic prednisone for flares Since that time, she has avoided hospitalization and disease has been more consistently in remission. Summary Refer to rheumatology early and treat aggressively Rheumatoid arthritis and inflammatory arthritis shorten the patient’s life expectancy if left untreated Many treatment options exist and treatment can be tailored to the patient’s needs.