A multicenter, open-label, pharmacokinetic/pharmacodynamic safety, and tolerability study of basiliximab (Simulect) in pediatric de novo renal transplant recipients.
BACKGROUND
Basiliximab (Simulect) has been shown to be safe and effective in adult renal transplant recipients, when used in combination with cyclosporine (Neoral) and corticosteroids. We report on the safety and preliminary efficacy of basiliximab in pediatric de novo renal transplant recipients.


METHODS
This was an open-label, 12-month study of basiliximab in 41 patients (2 cohorts: <9 and 9 to <16 years). In phase 1, two intravenous (IV) bolus injections of basiliximab (12 mg/m ) were administered (before and 4 days postsurgery). In phase 2, two injections (<40 kg, 10 mg and > or =40 kg, 20 mg) were administered at the same time points. Most patients (26/41 [63%]) received cadaveric kidneys. Almost half of the patients had three human leukocyte antigen mismatches with the organ donors. Concurrent immunosuppression included Neoral and corticosteroids. Azathioprine was allowed after 28 days.


RESULTS
All patients completed the 1-year study. The acute tolerability of basiliximab via IV bolus injection was good, without evidence of cytokine-release syndrome or acute local reactions. All patients experienced adverse events, but most (71%) were mild or asymptomatic. No deaths or malignancies occurred. The incidence and types of serious adverse events (59%) and serious infections (44%) were as expected in this patient population, and few were drug-related (7% and 5%, respectively). Thirty-eight patients (93%) had infections, mostly urinary tract infections, as expected for renal transplant patients. Six patients (15%) had drug-related adverse events. Biopsy-confirmed acute rejection episodes occurred in 6/41 (15%) of patients during the first 6 months posttransplantation and in 9/41 (22%) patients during the first 12 months. Five patients (12%) experienced graft loss, none of which were preceded by acute rejection episodes.


CONCLUSIONS
Basiliximab is safe and well tolerated when administered by IV bolus injection in de novo pediatric renal transplant recipients. These preliminary data suggest that basiliximab, given in combination with cyclosporine and corticosteroids, is an effective immunosuppressive regimen for the prevention of acute rejection in pediatric renal transplantation.
Offner
Gisela
G
Kinderklinik der Medizinische Hochschule, Hannover, Germany.
Broyer
Michel
M
Niaudet
Patrick
P
Loirat
Chantal
C
Mentser
Mark
M
Lemire
Jacques
J
Crocker
John F S
JF
Cochat
Pierre
P
Clark
Godfrey
G
Chodoff
Lawrence
L
Korn
Alexander
A
Hall
Michael
M
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use; D000077552:Basiliximab; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D015994:Incidence; D007223:Infant; D007275:Injections, Intravenous; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D011993:Recombinant Fusion Proteins; D012449:Safety; D013997:Time Factors
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D016572:Cyclosporine; D000077552:Basiliximab; D001379:Azathioprine