Basiliximab Combined with Low-Dose Rabbit Anti-Human Thymocyte Globulin

Abstract

In high-risk kidney transplant recipients, induction therapy with rabbit anti-human thymocyte globulin (RATG) reduces the risk for acute rejection but is associated with significant toxicity, opportunistic infections, and cancer. Using reduced doses of RATG combined with anti-IL-2 antibodies may achieve the same antirejection activity of standard-dose RATG but with a better safety profile. This randomized, open-label study compared the efficacy, tolerability, and costs of low-dose RATG (0.5 mg/kg per d) plus basiliximab (20 mg 4 d apart) versus standard-dose RATG (2 mg/kg per d) in 33 consecutive high-risk renal transplant recipients (living-related transplant recipients, sensitized patients or patients who received another transplant, and patients with delayed graft function) over 6 mo of follow-up. All patients received concomitant therapy with steroids, cyclosporin A, and azathioprine or mycophenolate mofetil. Seventeen patients received low-dose RATG plus basiliximab, and 16 received standard-dose RATG. Patient (100 versus 100%) and graft (94 versus 100%) survival were comparable in the two groups, but the incidence of fever (17.6 versus 56.5%; P ‫؍‬ 0.01), leukopenia (23.5 versus 56.3%; P < 0.05), anemia (29.4 versus 62.5%; P < 0.05), cytomegalovirus reactivations (17.6 versus 56.5%; P ‫؍‬ 0.01), the number of transfused units (0.5 ؎ 0.9 versus 2.0 ؎ 2.4; P < 0.001), and treatment costs (3652 ؎ 704 versus 5400 ؎ 1960 euro; P ‫؍‬ 0.001) were lower with low-dose RATG plus basiliximab than with standard-dose RATG. There was one episode of biopsy-proven acute rejection on low-dose RATG plus basiliximab, and there were two on standard-dose RATG. In renal transplantation, induction therapy with basiliximab plus low-dose RATG effectively prevents acute rejection and is safer and more cost-effective than induction with standard-dose RATG.

Titrating Rituximab to Circulating B Cells to Optimize Lymphocytolytic Therapy in Idiopathic Membranous Nephropathy

“…All patients were advised to have low sodium and controlled protein intake and received symptomatic treatment to control edema, hypertension, and dyslipidemia. Treatment targets were the same with the two regimens (8).…”

Autologous Mesenchymal Stromal Cells and Kidney Transplantation

“…All patients received induction regimen with basiliximab (20 mg intravenous pretransplant and on day 4 posttransplant) and low-dose rabbit antithymocyte globulin (RATG) infusion (thymoglobulin, 0.5 mg/ kg, daily from day 0 to day 6 posttransplant) as per center practice (25). Maintenance immunosuppression was with cyclosporine A (CsA, target trough blood levels of 300 to 400 ng/ml up to day 7 postsurgery, and 100 to 150 ng/ml at month 5 posttransplantation), mycophenolate mofetil (plasma trough mycophenolic acid [MPA] levels of 0.5 to 1.5 g/ml) (26), and steroids.…”

In Kidney Transplant Patients, Alemtuzumab but Not Basiliximab/Low-Dose Rabbit Anti-Thymocyte Globulin Induces B Cell Depletion and Regeneration, Which Associates with a High Incidence of De Novo Donor-Specific Anti-HLA Antibody Development

“…Since the day of transplant, reference patients received five consecutive rATG (thymoglobulin) infusions at a daily dose of 0.5 mg/ kg (12,13). The dose of rATG was reduced or temporary withdrawn when WBC or platelet counts decreased to ,2,000/ml or ,50,000/ml, respectively.…”

“…Induction therapy with very low-dose rATG combined with the mAb anti-IL-2R basiliximab (Bas), given with the aim of inhibiting the activity of T cells surviving the lymphocytolytic effect of rATG, prevented acute graft rejection in kidney transplant patients as effectively as did full-dose rATG monotherapy but with remarkably fewer side effects (12,13) and negligible risk for acute humoral rejection.…”