A multicenter, prospective, randomized, double-blind trial of basiliximab in heart transplantation.
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.
Mehra
Mandeep R
MR
Cardiomyopathy and Heart Transplant Center, Ochsner Clinic Foundation, New Orleans, Louisiana, USA. mmehra@ochsner.org
Zucker
Mark J
MJ
Wagoner
Lynne
L
Michler
Robert
R
Boehmer
John
J
Kovarik
John
J
Vasquez
Arthur
A
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D000077552:Basiliximab; D016572:Cyclosporine / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007239:Infections / Q000453:epidemiology; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011184:Postoperative Period; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D014481:United States
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D016572:Cyclosporine; D000077552:Basiliximab; D009173:Mycophenolic Acid; D008775:Methylprednisolone