Cyclosporin: a review of its pharmacology and clinical potential in the treatment of systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a complex multisystem disease which is characterised by formation of antibodies to ;self' antigens. It often presents as a mild, controllable disorder but may become severe and is potentially life threatening, particularly when major organs/systems are involved. Although treatments for severe SLE are available (e.g. corticosteroids +/- cytotoxic/immunosuppressive agents), high dose or long term therapy with these agents is associated with serious and potentially life-threatening adverse effects and is not effective in all patients. Several noncomparative trials in patients with severe SLE refractory to conventional treatment have demonstrated that low dose cyclosporin in combination with steroids (and occasionally with additional cytotoxic/immunosuppressive agents) can provide long term disease improvement or remission and, importantly, a reduction in steroid use. Clinical benefits have also been observed with the cyclosporin-steroid combination in patients with lupus nephritis, most of whom had failed to respond to conventional treatment. Nephrotoxicity has been documented in some patients receiving cyclosporin for SLE, but initial biopsy data suggest that this complication is not a treatment-limiting factor for most patients. Nevertheless, the risk of cyclosporin-induced nephrotoxicity and the clinical implications of this effect have yet to be accurately assessed in large numbers of patients with SLE and definitive data may be difficult to obtain. Although initial efficacy and tolerability data from patients with lupus nephritis are favourable, the drug is more likely to be used in patients whose kidney function remains relatively unimpaired. Thus, available noncomparative data suggest that cyclosporin is useful in the treatment of patients with severe refractory SLE or those who cannot tolerate conventional therapy, but definitive comparative data are lacking. Any decision to prescribe cyclosporin for such patients will need to take into account the potential benefits of the drug, the clinical implications of uncontrolled disease and the risk of nephrotoxicity in individual patients.
Noble
S
S
Adis International Limited, Auckland, New Zealand.
Wagstaff
A J
AJ