Basiliximab combined with low-dose rabbit anti-human thymocyte globulin: a possible further step toward effective and minimally toxic T cell-targeted therapy in kidney transplantation.
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.
Ruggenenti
Piero
P
Mario Negri Institute for Pharmacological Research, Via Gavazzeni 11, 24125 Bergamo, Italy.
Codreanu
Igor
I
Cravedi
Paolo
P
Perna
Annalisa
A
Gotti
Eliana
E
Remuzzi
Giuseppe
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000961:Antilymphocyte Serum / Q000008:administration & dosage* / Q000494:pharmacology; D000077552:Basiliximab; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D016030:Kidney Transplantation; D008297:Male; D010865:Pilot Projects; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D013601:T-Lymphocytes / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab