Safety aspects of cyclosporin in rheumatoid arthritis

While cyclosporin has an established role in the management of patients with rheumatoid arthritis, its use can be accompanied by various adverse events. In daily practice, the potential for cyclosporin to induce nephropathy is of most concern and has, to some extent, limited the use of this drug. However, these effects on renal function are dose dependent. Two international meetings have resulted in the publication of guidelines aimed at limiting the risk of adverse events when cyclosporin is used in patients with rheumatoid arthritis. The 1994 International Consensus guidelines with respect to renal safety recommend the principal dosage regimen of 'go low, go slow', which requires starting patients on a daily dose of between 2.5 and 3.5 mg/kg with the maximum daily dose not exceeding 5 mg/kg. The cyclosporin dosage chosen should be titrated against the highest acceptable increase in serum creatinine, i.e. a 30% increase over the baseline value. Renal biopsy data support these guidelines, and when the latter are followed by physicians, it is very unlikely that histological damage will occur. The new oral microemulsion-based formulation of cyclosporin (Neoral) has a more predictable absorption and a 20% greater bioavailability than the conventional formulation (Sandimmun). Therefore, the microemulsion formulation may enable more patients to receive effective treatment at lower doses. This could have interesting safety and pharmacoeconomic implications.