RA: Medical Management


- See:
       - Anti-inflammatory agents
       - Corticosteroids
       - Cyclosporin A
       - Sulfasalazine (anti folate activity)


- Remittive Agents:
    - salicylates
    - gold
            - gold salts (inhibit monocyte function)
            - side effects include thrombocytopenia, neutropenia, or proteinuria;
    - D-Penicillamine (modulate lymphocyte function)
    - azathioprine
    - cyclophosphamide


- Anti-inflammatory Agents:
    - these agents are are the foundation of drug therapy in rheumatoid arthritis;
    - nonsteroidal medications should not be stopped when second-line drugs are added to therapy;
            - cyclooxygenase inhibitors may diminish glomerular filtration rate and alter blood pressure in patients taking antihypertensive drugs;
    - aspirin:
            - aspirin therapy continues to be a useful agent in RA;
            - many patients tolerate it well without gastric distress, particularly when enteric-coated preparations are used;
            - in addition, use of salicylates enables physician to monitor compliance;
            - tests to measure serum salicylate levels are readily available;
            - tinnitus is a relatively harmless side effect, & gives indication that blood levels are approaching therapeutic values;


- Steroids: for Rheumatoid Arthritis


- Tumor Necrosis Factor Inhibitors


- Methotrexate:
    - approved for use in RA;
    - indicated for progressive or severe forms of RA;
    - now being used more often than gold salts or penicillamine;
    - expect improvement in symptoms of 25 to 40%, as compared with improvement in patients not taking drug, can be expected;
    - mechanism anti folate, immunosuppresive action;
    - dose: low-dose methotrexate (5-15 mg once weekly);
    - side-effects: hepatic and pulmonary toxicity;
    - interactions:
          - septra (bone marrow supression)
          - probenecid (blocks tubular secretion of methotrexate);


- Antimalarials
    - (stabilize lysosomal membranes and inhibit IL1)
    - antimalarials (stabilize lysosomal membranes, and inhibit IL 1)
    - hydroxychloroquine sulfate, is frequently the first of the second line agents to be used;
          - major side effect is macular degeneration;

- Leflunomide


- TNF Inhibitors:
    - these agents bind TNF and block inflammation by inhibiting the subsequent effects of this cytokine;
    - need to test for latent TB before initiating TNF therapy;
    - infliximab:
          - a chimeric monoclonal antibody against TNF-(alpha)
          - variable region of a murine antibody grafted to the constant region of a human antibody;
          - given intravenously every two months;
          - in the report by Lipsky PE, et al., the authors treated 428 patients who had active RA despite methotrexate therapy with placebo or infliximab;
                 - IV doses of 3 or 10 mg / kg of body weight q 4 or 8 weeks in combo w/ oral methotrexate for 54 weeks;
                 - the authors noted the combination of infliximab and methotrexate was well tolerated and resulted in a sustained reduction in the symptoms and signs of rheumatoid arthritis that was significantly greater than the reduction associated with methotrexate therapy alone (clinical response, 51.8 percent vs. 17.0 percent; P<0.001);
                 - the quality of life was also significantly better with infliximab plus methotrexate than w/ methotrexate alone;
                 - radiographic evidence of joint damage increased in the group given methotrexate, but not in the groups given infliximab and methotrexate (mean change in radiographic score, 7.0 vs. 0.6; P<0.001);
                 - radiographic evidence of progression of joint damage was absent in infliximab-treated patients whether or not they had a clinical response;
                 - the authors concluded the patients with persistently active RA despite methotrexate therapy, repeated doses of infliximab in combination with methotrexate provided clinical benefit and halted the progression of joint damage.
                 - ref: Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. 
    - etanercept (enbrel)
          - soluble receptor
          - dimer consisting of a TNF receptor joined to the Fc domain of a human IgG1 molecule;
          - given subcutaneously twice a week;
          - in the report by Bathon JM, et al (2000), the authors followed 632 patients with early RA with either twice-weekly subQ etanercept (10 or 25 mg) or weekly oral methotrexate (mean, 19 mg per week) for 12 months.
                  - as compared with patients who received methotrexate, patients who received the 25-mg dose of etanercept had a more rapid rate of improvement, with significantly more patients having 20 percent, 50 percent, and 70 percent improvement in disease activity during the first six months (P<0.05)
                  - among patients who received the 25-mg dose of etanercept, 72 percent had no increase in the erosion score, as compared with 60 percent of patients in the methotrexate group (P=0.007);
                  - this group of patients also had fewer adverse events (P=0.02) and fewer infections (P=0.006) than the group that was treated with methotrexate
                  - A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis.


References

Tumor Necrosis Factor Blockers in Rheumatoid Arthritis

A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis.

Disease-Modifying Agents and Experimental Treatments of Rheumatoid Arthritis.

Longterm treatment with nonsteroidal antiinflammatory drugs in rheumatoid arthritis: a prospective drug survival study.

Medical considerations and perioperative care for rheumatoid surgey.  

Infectious and healing complications after elective orthopaedic foot and ankle surgery during tumor necrosis factor-alpha inhibition therapy.



Original Text by Clifford R. Wheeless, III, MD.

Last updated by Data Trace Staff on Tuesday, August 21, 2012 2:24 pm