Anti-interleukin-2 receptor antibodies in transplantation: what is the basis for choice?
Two monoclonal antibody preparations against the alpha-chain of the interleukin-2 receptor (IL-2Ralpha) are available for use, basiliximab and daclizumab, a chimeric and a humanised antibody, respectively. The first clinical studies have demonstrated the efficacy of these agents as induction therapy to reduce the rate of acute rejection after organ transplantation. Basiliximab and daclizumab have a similar effect on prevention of acute rejection. Likewise, incidence of infections and malignancies are not different between the two treatment options. Anti-IL-2Ralpha therapy was very well tolerated in clinical trials. Phase III studies with basiliximab have been undertaken with a two-dose regimen, consisting of two doses of 20mg, in an attempt to saturate the IL-2Ralpha on peripheral blood T lymphocytes for an average of 4-6 weeks. In contrast, the daclizumab dose is corrected for bodyweight and the goal is to achieve IL-2Ralpha blockade for 12 weeks. Phase III efficacy trials with daclizumab have, therefore, been developed with five doses of 1 mg/kg every 2 weeks in the first 2 months after transplantation. Whether or not it is a benefit to have blockade of the IL-2Ralpha for 10-12 weeks (daclizumab) compared with 4-6 weeks (basiliximab) remains unknown. Assuming 4-6 weeks would be sufficient for prevention of acute rejection, many centres have changed the protocol of daclizumab administration to two doses, the first dose given at the time of transplantation, the second 10 or 14 days after, with good success. Therefore, it seems feasible to limit the dose of daclizumab, which increases the ease of administration and probably also the cost effectiveness of this agent. There are no controlled studies comparing basiliximab and daclizumab, nor have different dose regimens been directly compared in renal transplantation. The data available suggest the differences are small, if present at all, and it is unlikely that such a trial will ever be done. With both compounds, a significant reduction in the number of acute rejection episodes following solid organ transplantation can be obtained without an increase in adverse effects or infectious complications.
Department of Hospital Pharmacy, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands. t.vangelder@erasmusmc.nl
Teun
T
Van Gelder
Michiel
M
Warlé
Rik G
RG
Ter Meulen
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000077552:Basiliximab; D017326:Clinical Trials, Phase III as Topic; D000077561:Daclizumab; D016903:Drug Monitoring; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors* / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use; D014181:Transplantation Immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab; D000077561:Daclizumab