CLINICAL USE OF CYCLOSPORINE IN RHEUMATOID-ARTHRITIS

Rheumatoid arthritis is a chronic immune-mediated disease characterise d by an inflammatory synovitis and extra-articular manifestations, The re is an expanding body of evidence to indicate that the activation of T lymphocytes is central in the initiation and perpetuation of this d isease. Cyclosporin is an immunomodulator and a highly specific inhibi tor of T-lymphocyte function, and has demonstrated disease-modifying p roperties 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. Cyclospori n is lipophilic by nature and the conventional oral formulation (Sandi mmun(R)) was subject to incomplete and highly variable absorption, res ulting in substantial inter- and intrasubject variations in peak conce ntrations and systemic bioavailability. A microemulsion-based formulat ion of cyclosporin (Neoral(R))(1) has recently been developed, and pos sesses more predictable and improved absorption with a consequent incr eased peak concentration and systemic bioavailability. The improved pr edictability of absorption, and hence blood concentrations, facilitate s the ability to 'tailor' therapy to an individual patient, which, in theory, could translate into an improved efficacy and safety profile.