Use of sirolimus to facilitate steroid withdrawal from a cyclosporine regimen.

OBJECTIVE

Chronic steroid therapy has been associated with many comorbidities of transplant immunosuppression. Because sirolimus blocks one of the sites affected by steroids, we sought to examine whether substituting this drug mitigated these toxicities.

METHODS

We used intent-to-treat methodology to compare the clinical outcomes and laboratory results between 30 renal transplant recipients converted from steroids to sirolimus with a cohort of demographically matched subjects who were transplanted concurrently with the study group and maintained on steroids. All patients received ongoing cyclosporine-based immunosuppression. To compensate for pharmacokinetic interactions with sirolimus, the cyclosporine exposure was markedly reduced in the study group. Statistical comparisons utilized analysis of variance, chi-square tests, and log rank evaluation of Kaplan-Meier curves.

RESULTS

Conversion from prednisone to sirolimus was accomplished without difficulty in 27 of 30 patients. Treatment failures among the converted patients were due to chronic allograft nephropathy (n = 1), recurrence of original disease (n = 1), or chronic rejection (n = 2). By intent-to-treat analysis, the outcomes were similar in the study versus concurrent control groups. Laboratory values showed triglyceridemia as an adverse reaction to sirolimus, and reduced leukocytes, to steroid withdrawal. The observed clinical benefits solely reflected the markedly reduced cyclosporine exposure. Based on responses to a questionnaire administered prior to versus 12 and 24 months after steroid withdrawal, several domains revealed improvements in subjective complaints.

CONCLUSION

Conversion from prednisone to sirolimus in combination with cyclosporine was easily accomplished in most renal transplant recipients. Although a 2-year follow-up failed to reveal objective benefits of the maneuver (other than those consequent to reduced cyclosporine exposure), most patients reported a subjectively improved health status.