Topic: E. Clinical Pediatric Surgery/Transplantation/Endocrine/Plastics Surgery
A Randomized Double Blind, Placebo-Controlled Trial of Early Corticosteroid Cessation Versus Chronic Corticosteroids: Five Year Results
E. Steve Woodle
University of Cincinnati, Cincinnati, OH
Three double blind trials of corticosteroid withdrawal (CSWD) have previously been reported, however, they evaluated late CSWD (beyond three months) with short blinding periods (<1yr). The final results of a double blind placebo controlled trial with early CSWD (7 days posttransplant) and a five year blinding period are presented.
METHODS: CSWD (n=191 patients) was compared to chronic corticosteroid maintenance (CCS, n=195 patients) under tacrolimus/mycophenolate with either thymoglobulin (Thymo) or IL-2R antibody (Ab). The composite primary endpoint included death, graft loss or severe acute rejection (AR) (requiring Ab treatment or Banff 97 Grade >2A). Prednisone dose in controls was 5mg/day after 6 months.
RESULTS: Data is presented as CCS/CSWD. No differences occurred in primary endpoint (13.3%/15.7%); death (6.2%/5.2%); death-censored graft loss (3.6%/5.2%), or severe AR (5.1%/7.9%). Death to infection was higher with CCS 2.6%/0%, p=0.05). AR approached significance (10.8%/17.8%, p=0.06). No differences in renal function occurred: serum creatinine (1.5+0.8/1.6+0.7 mg/dl); calculated creatinine clearance (60.2+20.5/57.3+20.25 ml/min/1.73m2; patients with creatinine clearance <40 ml/min (7.4%/10.8%). An absolute increase in chronic allograft nephropathy of 5.8% occurred with CSWD (4.1%/9.9%, p=0.03), however, overall graft survival was not different. CSWD provided cardiovascular risk/metabolic benefits: posttransplant diabetes requiring insulin (13.5%/2.1%, p=0.01); change in triglycerides (-27.1 / -54.5 mg/dl), and bone disorders (fractures/avascular necrosis) (11.3%/4.7%, p=0.02).
CONCLUSIONS: Final five year results indicate that: early CSWD provides cardiovascular risk and bone disease benefits without significant effects on kidney allograft survival and function. It is important to note that these differences were observed despite the low daily prednisone dose in controls.