Rheumatoid arthritis. Several randomized controlled trials have demonstrated efficacy of cyclosporine in RA. The first reported success of combination therapy was achieved by adding cyclosporine to methotrexate. Patients with rheumatoid arthritis who did not respond to a maximum dose of methotrexate (15 mg/wk) were treated with the addition of cyclosporine at a mean dosage of 2.97 mg/kg of body weight per day. Clinically meaningful improvements were observed. Transient increases in serum creatinine concentration were frequently reported in patients taking cyclosporine, but these values returned to the normal range when the dose of the drug was adjusted. However, an increase in serum creatinine concentration that is sustained longer than 3 months can be associated with permanent residual loss of renal function. Daily doses of cyclosporine that exceed 4 mg/kg are associated with biopsy-proven...