Sandimmun (cyclosporin A): mode of action and clinical results in rheumatoid arthritis.
Cyclosporin A (Sandimmun) has gained wide acceptance by most transplant physicians as the immunosuppressant of choice for preventing rejection of solid organ grafts and graft-versus-host disease. The drug has a specific effect on T-lymphocytes in which it seems to prevent the transcription of genes for several lymphokines. The reduction in IL-2 prevents the clonal expansion of T-lymphocytes and their differentiation into effector T-cells. The reduction in IFN-tau interrupts the feedback mechanism between T-cells and macrophages and the aberrant expression of MHC class II molecules. Through these mechanisms Sandimmun exerts an immunosuppressive and anti-inflammatory effect. Considerable evidence has accumulated to suggest that rheumatoid arthritis (RA) is an auto-immune disease. Activated T-lymphocytes interrelate with macrophages, other inflammatory cells and effector cells in joint tissue, leading to symptoms of inflammation accompanied by joint destruction. Immunosuppressive treatment is already well established in this disease and several trials have already taken place using Sandimmun. A total of 224 patients with RA refractory to conventional disease-modifying drugs have participated in 11 published clinical studies. A review of these studies concludes that Sandimmun is efficacious in controlling inflammatory and functional symptoms, although this improvement is no generally accompanied by reductions in ESR and rheumatoid factor. The frequency of adverse events is comparable to that of other treatments but nephropathy remains the principal factor limiting the use of Sandimmun. Recent evidence suggests that with a strict dosage strategy and good monitoring this problem is controllable and reversible. Further studies are under way to confirm these claims.
Shand
N
N
Clinical Department, Sandoz Ltd, Basle, Switzerland.
Richardson
B
B
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000097:blood; D003524:Cyclosporins / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced
D003524:Cyclosporins; D002097:C-Reactive Protein