Agents for Rheumatoid Arthritis

HPI SM is a 35-year-old woman with a diagnosis of rheumatoid arthritis (RA). She suffers from morning stiffness, fatigue, and generalized muscle and joint pain. She has had to limit her physical activity and is unable to wear her rings because of finger swelling. Her current treatment plan includes education and physical therapy. 

What are the pharmacological differences between NSAIDs and disease-modifying antirheumatic drugs (DMARDs)  

What are the toxicities associated with NSAIDs and DMARDs  

Rheumatoid arthritis is a chronic, inflammatory, autoimmune disease of unknown etiology that if left untreated results in progressive joint destruction, deformity, disability, and premature death. Theories of possible etiologies include genetic, hormonal, viral, autoimmune, and environmental factors. The disease peaks between the fourth through sixth decades of life and is two to three times more common in women than in men. Differences in prevalence rates between ethnic groups are small. 

The pathogenesis of RA is a combination of cellular (e.g., macrophages, lymphocytes), biochemical (e.g., prostaglandins, cytotoxins) and mechanical factors that promote the inflammatory condition of the synovial lining. The normal anatomy 

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KUnkhoff A. Biological agents for rheumatoid arthritis. Drugs 2004 64 1267-83. 

Puvion-Dutilleul F, Puvion E. Human parvovirus B19 as a causative agent for rheumatoid arthritis. Proc Nat Acad Sci USA. 1998 95 8227-8232. 

The notion of handedness in physical science arose from John Frederick William Herschel s descriptions (2) of quartz. (Parenthetically, it is worth noting here his discovery of the complexation of silver ions by thiosulfate and his comment that the resulting solutions tasted sweet. The eutropic [Au(S203)2] is also bioactive in "myochrysin", the chrysotherapeutic agent for rheumatoid arthritis.) The now well developed relationship between shape and chiroptical spectroscopy has roots in the... 

Hydroxychloroquine Plaquenil) and chloroquine Ara-len) are 4-aminoquinoline antimalarial drugs that possess modest DMARD activity. They are indicated for the treatment of rheumatoid arthritis and systemic lupus erythematosus their use as antimalarials is detailed in Chapter 53. The onset of action of these drugs is longer than that of other DMARDs, and their side effects are relatively mild. Because of this, these agents show promise as ingredients of combination therapies for rheumatoid arthritis. 

Originally developed for chemotherapy, azathioprine is used today mainly as an immunosuppressive agent and rarely as an antineoplastic drug. It was introduced as an immunosuppressive agent by a British pioneer of tissue transplantation, Roy Caine. Azathioprine was used to prevent rejection after tissue transplantation as a replacement for 6-mercaptopurine because it was less toxic. In addition to tissue transplantation, it is also used for rheumatoid arthritis and Crohn s disease. Azathioprine is a prodrug which in the body is converted to its active metabolites 6-mercaptopurine and 6-thioinosinic acid. Until the discovery of cyclosporine, azathioprine in combination with steroids was the standard treatment to prevent rejection after tissue transplantation. 

Originally developed as part of a large-scale effort headed by the United States National Cancer Institute to investigate chemotherapeutic agents from natural sources, paclitaxel was approved by the FDA in 1992 as an antineoplastic agent to treat metastatic ovarian cancer after failure of first-line or subsequent chemotherapy (37). Further studies demonstrated efficacy in other solid tumors (38). In addition, paclitaxel was shown to inhibit T- and B-cell proliferation when tested for transplant-rejection application (39,40) and has demonstrated inhibition of matrix-metalloproteinase synthesis in studies conducted to test its utility for rheumatoid arthritis (41). 

Sulfasalazine is also used as a disease-modifying agent in rheumatoid arthritis (see p. 292), the condition for which it was originally introduced in the 1930s. It is available as a tablet, retention enema or suppository. 

Proresid (mitopodozide), a mixture of more than 20 derivatives of Podophyllum emodi, has been used for many years in some countries as a disease-modifying agent in rheumatoid arthritis. A microtubuhn antagonist, it is comparable with colchicine and griseofulvin. Its use has been limited because treatment is often comphcated by severe diarrhea, abdominal pain, nausea, and vomiting. Leukopenia and thrombocytopenia have been reported (3,4). 

Fenoprofen is a NSAID agent, which decreases inflammation, pain, and fever, probably through inhibition of cyclooxygenase activity and prostaglandin synthesis. It is indicated in the symptomatic relief for rheumatoid arthritis, osteoarthritis, and mild to moderate pain. 

AstraZeneca currently have one agent, AZD-5672 (structure not disclosed) in Phase 2 clinical trials for rheumatoid arthritis, kidney function and atherosclerosis. 

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