Rheumatoid arthritis cyclosporine

Cyclospasmol cyclandelate. cyclosporin [ban] (ciclosporin [inn.jan] cyclosporine [usan] cyclosporin A Neoral Sandimmune ) is a cyclic polypeptide ANTIBIOTIC, possessing IMMUNOSUPPRESSIVE properties (with a specific action on T-lymphocytes). It also has ANTIFUNGAL activity and can be used clinically as an immunosuppressant after transplant surgery, and to treat severe autoimmune diseases including rheumatoid arthritis, cyclosporin A cyclosporine, cyclothiazide [ban. inn. usan] is a (thiazide) diuretic which can be used in ANTIHYPERTENSIVE therapy, cyclovalone [inn] (DVC) is a cyclohexanone, a choleretic... 

In rheumatoid arthritis, cyclosporine is used in severe cases that have not responded to methotrexate. Cyclosporine can be combined with methotrexate, but the levels of both drugs must be monitored closely. In psoriasis, cyclosporine is indicated for treatment of adult immunocompetent patients with severe and disabling disease for whom other systemic therapies have failed. Because of its mechanism of action, cyclosporine also has been used successfully in inflammatory bowel disease see Chapter 38). 

The first human kidney and bone marrow transplants using cyclosporine were reported in 1978. Oral or intravenous cyclosporine is an immunosuppressant for transplantation of these and other organs and investigations are underway for its possible use in a variety of autoimmune diseases including rheumatoid arthritis, severe psoriasis, and Crohn s disease. Dose-dependent nephrotoxicity (261—264) remains the primary limitation of the dmg and necessitates close monitoring of patients, including measurement of dmg levels in blood. Cyclosporine research has been reviewed (265—274). 

Cyclosporine appears to have promise in the treatment of autoimmune diseases. It has a beneficial effect on the course of rheumatoid arthritis, uveitis, insulin-dependent diabetes, systemic lupus erythematosus, and psoriatic arthropathies in some patients. Toxicity is more of a problem in these conditions than during use in transplantation, since higher doses of cyclosporine are often required to suppress autoimmune disorders. 

Azathioprine also has applications in certain disorders with autoimmune components, most commonly rheumatoid arthritis. It is as effective as cyclophosphamide in the treatment of Wegener s granulomatosis. It has largely been replaced by cyclosporine in immunosuppressive therapy. Relative to other cytotoxic agents, the better oral absorption of azathioprine is the reason for its more widespread clinical use. 

Cyclosporin is usually given orally, although absorption is often unpredictable. The intravenous route is usually restricted to patients who cannot take the drug orally, because of the risk of anaphylactic reactions. Other uses of cyclosporin include psoriasis and severe, active rheumatoid arthritis when these do not respond to conventional treatment, and steroid-resistant nephrotic syndrome. 

Cyclosporine is approved for use in rheumatoid arthritis and retards the appearance of new bony erosions. Its usual dosage is 3-5 mg/kg/d divided into two doses. Anecdotal reports suggest that it may be useful in systemic lupus erythematosus, polymyositis and dermatomyositis, Wegener s granulomatosis, and juvenile chronic arthritis. 

Gerards AH et al Cyclosporine A monotherapy versus cyclosporine A and methotrexate combination therapy in patients with early rheumatoid arthritis A double blind randomised placebo controlled trial. Ann Rheum Dis 2003 62 291. [PMID 12634224]... 

Cyclosporine is used to prevent organ rejection after tissue transplantation. It is also used for rheumatoid arthritis, psoriasis and dry eyes (keratoconjunctivitis sicca). For... 

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. 

Because of the autoimmune basis of rheumatoid arthritis, various other drugs that affect the immune response are used on a limited basis. For instance, cyclosporine (Sandimmune), an immunosuppressant agent that is used to prevent rejection of organ transplants (see Chapter 37), is sometimes used to treat... 

Cyclosporine Neoral, Sandimmune Kidney, liver, heart, lung, pancreas, bone marrow Psoriasis, rheumatoid arthritis, nephrotic syndrome... 

Cyclosporine is used to a somewhat lesser extent in treating autoimmune diseases, but it may be helpful in conditions such as psoriasis, rheumatoid arthritis, inflammatory bowel disease, and glomerulonephri-tiS.i5,32,63 as discussed in Chapter 32, cyclosporine has also been used in the early stages of type 1 diabetes mellitus to help control immune-mediated destruction of pancreatic beta cells, thus decreasing the severity of this disease in some patients.9... 

Gremese E, Ferraccioli GF. Benefit/risk of cyclosporine in rheumatoid arthritis. Clin Exp Rheumatol. 2004 22(suppl 35) S101-S107. 

Stein CM, Kinirons MT, Pincus T, et al. Comparison of the dapsone recovery ratio and the erythromycin breath test as in vivo probes of CYP3A activity in patients with rheumatoid arthritis receiving cyclosporine. Clin Pharmacol Ther 1996 59 47-51. 

J.P. Branthwaite, and A. Nicholls, Cyclosporin and diclofenac interaction in rheumatoid arthritis. Lancet 337 252, 1991. 

Cyclosporine is an important drug in preventing rejection after kidney, hver, heart and other organ transplantation (Haberal et al., 2004). Cyclosporine usually is combined with other immunosuppressives especially glucocorticoids and either azathioprine or mycophenolate mofedl and sirolimus (Krensky et al., 2005). In renal alio transplants it has improved graft acceptance in most clinics to 95 percent. In addition to its use in transplantation cyclosporine is used for the treatment of a number of autoimmune diseases. In autoimmune diseases, as might be anticipated, cyclosporine is most effective in those which are T cell mediated. These include several forms of psoriasis, rheumatoid arthritis refractive to all other therapy, uveitis, nephrotic syndrome and type I diabetes mellitus. 

Landewe RB, Goei The HS, van Rijthoven AW, Rietveld JR, Breedveld FC, Dijkmans BA. Cyclosporine in common clinical practice an estimation of the benefit/ risk ratio in patients with rheumatoid arthritis. J Rheumatol 1994 21(9) 1631-6. 

Arellano F, Krupp P. Malignancies in rheumatoid arthritis patients treated with cyclosporin A. Br J Rheumatol 1993 32(Suppl l) 72-5. 

Kovarik JM, Mueller EA, Gerbeau C, Tarral A, Francheteau P, Guerret M. Cyclosporine and nonsteroidal antiinflammatory drugs exploring potential drug interactions and their imphcations for the treatment of rheumatoid arthritis. J Qin Pharmacol 1997 37(4) 336-43. 

Kovarik JM, Kurki P, Mueller E, Guerret M, Markert E, Alten R, Zeidler H, Genth-Stolzenburg S. Diclofenac combined with cyclosporine in treatment refractory rheumatoid arthritis longitudinal safety assessment and evidence of a pharmacokmetic/dynamic mteraction. J Rheumatol 1996 23(12) 2033-8. 

Weinblatt ME, Germain BE, Kremer JM,Wall BA,Weisman MH, Maler AL,Coblyn JS. Lack of a renal-protective effect of misoprostol In rheumatoid arthritis patients receiving cyclosporin A. Results of a randomized, placebo-controlled trial. Arthritis Rheum 1994 37 1321-1325. 

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