- 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 PE. Lipsky et al. N Engl J Med 2000;343:1594-602, 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.
Peter E. Lipsky et al. N Engl J Med 2000;343:1594-602
-
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 JM Bathon et al (NEJM, Nov 30, 2000 Vol. 343, No. 22), 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;
Tumor Necrosis Factor Blockers in Rheumatoid Arthritis
David S. Pisetsky, M.D., Ph.D. The New England Journal of Medicine -- March 16, 2000 -- Vol. 342, No. 11
A Comparison of Etanercept and Methotrexate in Patients with Early Rheumatoid Arthritis
Joan M. Bathon
JM Bathon et al (NEJM, Nov 30, 2000 Vol. 343, No. 22)
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.
S. Schneller.
Hand Clinics. Vol 5. 1989. p 115-126.
Infectious and healing complications after elective orthopaedic foot and ankle surgery during tumor necrosis factor-alpha inhibition therapy.
