BACKGROUND: The role and pharmacokinetics of interleukin-2 (IL-2) monoclonal antibodies (mAbs) in heart transplantation remain unclear. This 1-year double-blind, randomized, placebo-controlled study evaluated safety, tolerability, and pharmacokinetics of the IL-2 mAb basiliximab with cyclosporine, mycophenolate mofetil, and steroids in adult de novo heart transplant recipients. METHODS: Fifty-six patients received either basiliximab (20 mg) or placebo on Days 0 and 4 post-transplantation. Safety assessments included adverse events, serious adverse events, and infections. The time to and severity of biopsy-proven acute rejection (BPAR) were also assessed. RESULTS:Basiliximab was generally well tolerated. There were no significant differences between treatment groups with respect to adverse event profiles, serious adverse events (84.0% vs 61.3%), or infections (84% vs 74.2%). The mean number of days to first BPAR was longer with basiliximab (73.7 +/- 59.68) than placebo (40.6 +/- 53.30) at 6 months, but not statistically significant (trend). The duration that basiliximab concentrations exceeded the CD25 saturation threshold averaged 38 +/- 13 days. Patients with rejection did not clear basiliximab faster or have shorter durations of saturation than rejection-free patients. None of the patients screened had detectable anti-idiotype antibodies. CONCLUSIONS: These pilot results describe the pharmacokinetics of basiliximab and show that basiliximab appears to be tolerated with a similar safety profile to placebo in adult de novo heart transplant recipients. Larger scale clinical trials are feasible and warranted.
RCT Entities:
BACKGROUND: The role and pharmacokinetics of interleukin-2 (IL-2) monoclonal antibodies (mAbs) in heart transplantation remain unclear. This 1-year double-blind, randomized, placebo-controlled study evaluated safety, tolerability, and pharmacokinetics of the IL-2 mAb basiliximab with cyclosporine, mycophenolate mofetil, and steroids in adult de novo heart transplant recipients. METHODS: Fifty-six patients received either basiliximab (20 mg) or placebo on Days 0 and 4 post-transplantation. Safety assessments included adverse events, serious adverse events, and infections. The time to and severity of biopsy-proven acute rejection (BPAR) were also assessed. RESULTS:Basiliximab was generally well tolerated. There were no significant differences between treatment groups with respect to adverse event profiles, serious adverse events (84.0% vs 61.3%), or infections (84% vs 74.2%). The mean number of days to first BPAR was longer with basiliximab (73.7 +/- 59.68) than placebo (40.6 +/- 53.30) at 6 months, but not statistically significant (trend). The duration that basiliximab concentrations exceeded the CD25 saturation threshold averaged 38 +/- 13 days. Patients with rejection did not clear basiliximab faster or have shorter durations of saturation than rejection-free patients. None of the patients screened had detectable anti-idiotype antibodies. CONCLUSIONS: These pilot results describe the pharmacokinetics of basiliximab and show that basiliximab appears to be tolerated with a similar safety profile to placebo in adult de novo heart transplant recipients. Larger scale clinical trials are feasible and warranted.
Authors: H Haddad; D Isaac; J F Legare; P Pflugfelder; P Hendry; M Chan; B Cantin; N Giannetti; S Zieroth; M White; W Warnica; K Doucette; V Rao; A Dipchand; M Cantarovich; W Kostuk; R Cecere; E Charbonneau; H Ross; N Poirier Journal: Can J Cardiol Date: 2009-04 Impact factor: 5.223