Current concepts in clinical therapeutics: disease-modifying drugs for rheumatoid arthritis.
The epidemiology, pathophysiology, clinical features, diagnosis, and clinical course of rheumatoid arthritis (RA) and the role of disease-modifying antirheumatic drugs (DMARDs) in its treatment are reviewed. RA, a widespread disease affecting people of all races and sexes around the world, has an unknown and perhaps multifactorial etiology. Conflicting evidence supports an immune-complex, infectious, metabolic, or genetic basis for RA. The disease affects diarthrodial joints and begins as an immune response to unknown antigenic stimuli. A proliferative process ensues, leading to formation of a vascular lesion called a pannus, which then infiltrates into cartilage, subchrondral bone, and tendon. This destructive phase leads to classic RA symptoms of pain, limitation of motion, swelling, heat, and redness of the affected joint. Symptoms and laboratory tests form the basis for diagnosis. For most RA patients, conservative therapy provides substantial benefit. In those patients who suffer from unrelenting and progressively destructive disease, more aggressive intervention is necessary to prevent permanent disability. The DMARDs are reserved for treatment of this group of patients. DMARDs include such diverse agents as the gold compounds aurothioglucose, auranofin, and gold sodium thiomalate; the antimalarials hydroxychloroquine sulfate and chloroquine phosphate; penicillamine; and the cytotoxic agents azathioprine, methotrexate, and cyclophosphamide. DMARDs are effective but toxic therapeutic agents. Because of the toxicities of these agents, careful monitoring at regular intervals is necessary throughout the duration of therapy. For patients in whom these drugs demonstrate efficacy and are tolerated, the DMARDs may attenuate the disabling effects of long-term erosive disease.
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Department of Pharmacy, Thomas Jefferson University Hospital, Philadelphia, PA.
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D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000962:Antimalarials / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology; D001379:Azathioprine / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects; D003520:Cyclophosphamide / Q000627:therapeutic use; D004064:Digestive System / Q000187:drug effects; D005260:Female; D006046:Gold / Q000627:therapeutic use; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D007596:Joints / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D010396:Penicillamine / Q000627:therapeutic use; D011379:Prognosis; D013585:Synovitis / Q000473:pathology
D000305:Adrenal Cortex Hormones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000962:Antimalarials; D006680:HLA Antigens; D006046:Gold; D003520:Cyclophosphamide; D010396:Penicillamine; D001379:Azathioprine; D008727:Methotrexate