Basiliximab (Simulect???) is Efficacious in Reducing the Incidence of Acute Rejection Episodes in Renal Allograft Patients: Results at 12 Months

Abstract

1 In a randomized, double-blind Phase III study at 21 US transplant centers, we compared basiliximab (Simulect™) vs. placebo, in combination with cyclosporine microemulsion (Neoral®) and steroids, for the prevention of acute rejection in adult recipients of first cadaveric or living-donor renal allograft (≥1 HLA mismatch). Analyses at 6 and 12 months post transplantation are complete. Results: Patients were randomized to receive basiliximab 40mg (20mg Day 0 + 20mg Day 4), to provide CD25 suppression for 4-6 weeks (n=174), or placebo (n=174). Three hundred forty six patients were eligible for intent-to-treat (ITT) analysis (basiliximab 173; placebo 173), of whom 332 patients (basiliximab 166; placebo 166) completed the 12 month assessment period. No demographic differences were noted between the treatment groups. Efficacy: Addition of basiliximab to baseline dual immunosuppressive therapy reduced the incidence of first acute rejection by 33% (basiliximab 35% vs. placebo 52%, p=0.002) during the first 6 months post-transplant, and by 31% (38% vs. 55%, p=0.001) during the first 12 months. At 12 months, basiliximab-treated patients experienced fewer second rejections (12% vs. 23%, p=0.005), fewer biopsy-confirmed rejection episodes (35% vs. 49%, p=0.009), and fewer rejection episodes requiring treatment with augmented immunosuppression other than steroids (25% vs. 42%, p=0.001). Pharmacokinetics/Pharmacodynamics:Receptor saturating concentrations of basiliximab (≥0.2 µg/ml) in 164 patients was maintained for 36±14 days (range 12-91 days) post-transplant. Duration of CD25 suppression did not differ between patients with one or more acute rejection episodes compared to those who remained free of acute rejection (34±14 vs. 37±14 days, p=0.2718). Thus extended periods of IL-2R blockade (up to 3 months) did not confer an immunoprophylactic advantage compared to shorter periods of receptor suppression. Safety: Patient/graft survival at 12 months was 97%/95% for basiliximab-treated patients vs. 96%/93% for placebo (p=NS). Graft loss at 12 months was significantly reduced in Black patients (basiliximab: 1/47 (2%) vs. placebo: 7/59 (12%), p=0.032). The overall incidence and pattern of adverse events and infections did not differ between the treatment groups. Basiliximab was well-tolerated; no cytokine release syndrome was reported. Anti-idiotype antibodies were not detected. One PTLD occurred in a placebo-treated patient vs. none among patients in the basiliximab group. Conclusion: Basiliximab 40mg (20mg on Day 0 + Day 4) in combination with Neoral® and steroids reduces the incidence of acute rejection by 31% during the first 12 months after renal transplantation with an adverse events profile comparable to placebo.