Clinical use of cyclosporin in rheumatoid arthritis

Rheumatoid arthritis is a chronic immune-mediated disease characterised by an inflammatory synovitis and extra-articular manifestations. There is an expanding body of evidence to indicate that the activation of T lymphocytes is central in the initiation and perpetuation of this disease. Cyclosporin is an immunomodulator and a highly specific inhibitor of T-lymphocyte function, and has demonstrated disease-modifying properties in clinical studies in patients with rheumatoid arthritis. A concern with the use of cyclosporin has been the development of dose-dependent adverse effects, in particular renal dysfunction. Cyclosporin is lipophilic by nature and the conventional oral formulation (Sandimmun) was subject to incomplete and highly variable absorption, resulting in substantial inter- and intrasubject variations in peak concentrations and systemic bioavailability. A microemulsion-based formulation of cyclosporin (Neoral) has recently been developed, and possesses more predictable and improved absorption with a consequent increased peak concentration and systemic bioavailability. The improved predictability of absorption, and hence blood concentrations, facilitates the ability to 'tailor' therapy to an individual patient, which, in theory, could translate into an improved efficacy and safety profile.