Reduction of the occurrence of acute cellular rejection among renal allograft recipients treated with basiliximab, a chimeric anti-interleukin-2-receptor monoclonal antibody

Background. A double-blind, placebo-controlled phase III study was performe d to assess whether basiliximab, a chimeric anti-interleukin-a receptor mon oclonal antibody, reduced the incidence of acute rejection episodes in rena l allograft recipients. Methods. A total of 348 patients were randomized into two demographically m atched, equally sized groups treated with either basiliximab or placebo. Th e dose of basiliximab-20-mg infusions on day 0 and day 4-was selected to bl ock detection of interleukin-a receptor on 97% of peripheral blood lymphocy tes for 30-45 days. All patients received immunosuppressive therapy with cy closporine microemulsion (Neoral(R)) and steroids. An intent-to-treat analy sis of 1-year data assessed the incidence of posttransplant acute rejection episodes, patient and graft survival rates, and the safety and tolerabilit y of basiliximab. Results. Among the eligible 346 patients equally divided into the two treat ment groups, basiliximab reduced the proportion of patients who experienced biopsy-confirmed acute rejection episodes by 28%: 61 (35.3%) basiliximab v s. 85 (49.1%) placebo (P=0.009). Graft losses occurred in 9 (5.2%) basilixi mab-treated and 12 (6.9%) placebo-treated patients. Five (2.9%) deaths in t he basiliximab group and seven (4.0%) in the placebo group occurred. Compar ed with placebo, a higher fraction of basiliximab patients produced urine i n the operating room, and a significantly lower fraction had renal dysfunct ion in the first month (serum creatinine greater than or equal to 5 mg/dl) and between 1 and 12 months (serum creatinine greater than or equal to 3 mg /dl). During the first 12 months, 94 (54%) basiliximab-treated patients exp erienced serious adverse events, compared with 106 (61%) who received place bo. Conclusions. Prophylactic basiliximab therapy is well tolerated, has an adv erse event profile comparable to placebo, and significantly reduces the num ber of acute rejection episodes in renal allograft patients within the firs t year after transplantation.