Lancet 1997 Oct 25;350(9086):1193-8

Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group.

Nashan B, Moore R, Amlot P, Schmidt AG, Abeywickrama K, Soulillou JP
Medizinische Hochschule Hannover, Germany. nashan@TX-Amb.MH-Hannover.DE 

Abstract
BACKGROUND: Currently available immunosuppressive regimens for cadaver-kidney
recipients are far from ideal because acute-rejection episodes occur in about
30% to 50% of these patients. In the phase III study described here we assessed
the ability of basiliximab, a chimeric interleukin (IL)-2 receptor monoclonal
antibody, to prevent acute-rejection episodes in renal allograft recipients.
METHODS: 380 adult recipients of a primary cadaveric kidney transplant were
randomly allocated, in this double-blind trial, to receive a 20 mg infusion of
basiliximab on day 0 (day of surgery) and on day 4, to provide IL-2-receptor
suppression for 4-6 weeks (n=193), or to receive placebo (n=187). Both groups
received baseline dual immunosuppressive therapy with cyclosporin and steroids
throughout the study. The primary outcome measure was incidence of
acute-rejection episodes during the 6 months after transplantation. Safety and
tolerability were monitored over the 12 months of the study. FINDINGS: 376
patients were eligible for intention-to-treat analysis (basiliximab, n=190;
placebo, n=186). No significant differences in patient characteristics were
apparent. The incidence of biopsy-confirmed acute rejection 6 months after
transplantation was 51 (29.8%) of 171 in the basiliximab group compared with 73
(44.0%) of 166 in the placebo group (32% reduction; 14.2% difference [95%
Kaplan-Meier CIs 3% to 24%], p=0.012). The incidence of steroid-resistant first
rejection episodes that required antibody therapy was significantly lower in the
basiliximab group (10% vs 23.1%, 13.1% difference [5.4% to 20.8%], p<0.001). At
weeks 2 and 4 post-transplantation, the mean daily dose of steroids was
significantly higher in the placebo group (p<0.001 with one-way analysis of
variance). The incidence of graft loss at 12 months post-transplantation was 23
(12.1%) of 190 in the basiliximab group and 25 (13.4%) of 186 in the placebo
group (1.3% difference [-5% to 9%], p=0.591). The incidence of infection and
other adverse events was similar in the two treatment groups. The acute
tolerability of basiliximab was excellent, with no evidence of cytokine-release
syndrome. 14 deaths (basiliximab n=9; placebo n=5; -2.0% difference [-6% to 2%],
p=0.293) occurred during the 12-month study and a further three deaths
(basiliximab n=1; placebo n=2) occurred within the 380-day cut-off period. One
post-transplantation lymphoproliferative disorder was recorded in each group.
INTERPRETATION: Prophylaxis with 40 mg basiliximab reduces the incidence of
acute rejection episodes significantly, with no clinically relevant safety or
tolerability concerns