Skip to main content
SpringerLink
Log in

Anti-Interleukin-2 Receptor Antibodies in Transplantation

What is the Basis for Choice?

  • Current Opinion
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Two monoclonal antibody preparations against the α-chain of the interleukin-2 receptor (IL-2Rα) 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-2Rα 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-2Rα 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-2Rα 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-2Rα 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hariharan S, Johnson CP, Bresnahan BA, et al. Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Engl J Med 2000; 342: 605–12

    Article  PubMed  CAS  Google Scholar 

  2. Waldmann TA. The multichain interleukin-2 receptor: a target for immunotherapy. Ann Intern Med 1992; 116: 148–60

    PubMed  CAS  Google Scholar 

  3. Waldmann TA, O’Shea J. The use of antibodies against the IL-2 receptor in transplantation. Curr Opin Immunol 1998; 10: 507–12

    Article  PubMed  CAS  Google Scholar 

  4. Thaczuk J, Yu CL, Baksh S, et al. Effect of anti-IL-2Rα antibody on IL-2-induced Jak/STAT signaling. Am J Transplant 2002; 2: 31–40

    Article  Google Scholar 

  5. Vincenti F, Nashan B, Light S, et al. Daclizumab: outcome of phase III trials and mechanism of action. Transpl Proc 1998; 30: 2155–8

    Article  CAS  Google Scholar 

  6. Adu D, Cockwell P, Ives NJ, et al. Interleukin-2 receptor monoclocal antibodies in renal transplantation: meta-analysis of randomised trials. BMJ 2003; 326: 789–94

    Article  PubMed  CAS  Google Scholar 

  7. Webster AC, Playford EG, Higgins G, et al. Interleukin 2 receptor antagonists for renal transplant recipients: a meta-analysis of randomized trials. Transplantation 2004; 77: 166–76

    Article  PubMed  CAS  Google Scholar 

  8. Ahsan N, Holman MJ, Jarowenko MV, et al. Limited dose monoclonal IL-2R antibody induction protocol after primary kidney transplantation. Am J Transplant 2002; 2: 568–73

    Article  PubMed  CAS  Google Scholar 

  9. Bumgardner GL, Hardie I, Johnson RW, et al. Results of 3-year phase III clinical trials with daclizumab prophylaxis for prevention of acute rejection after renal transplantation. Transplantation 2001; 72: 839–45

    Article  PubMed  CAS  Google Scholar 

  10. Moser MAJ. Options for induction immunosuppression in liver transplant recipients. Drugs 2002; 62: 995–1011

    Article  PubMed  CAS  Google Scholar 

  11. Niemeyer G, Koch M, Light S, et al. Long-term safety, tolerability and efficacy of daclizumab (Zenapax) in a two-dose regimen in liver transplant recipients. Am J Transplant 2002; 2: 454–60

    Article  PubMed  CAS  Google Scholar 

  12. Beniaminovitz A, Itescu S, Lietz K, et al. Prevention of rejection in cardiac transplantation by blockade of the interleukin-2 receptor with a monoclonal antibody. N Engl J Med 2000; 342: 613–9

    Article  PubMed  CAS  Google Scholar 

  13. Przepiorka D, Kernan NA, Ippoliti C, et al. Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host-disease. Blood 2000; 95: 83–9

    PubMed  CAS  Google Scholar 

  14. Jacobsohn DA, Vogelsang GB. Novel pharmacotherapeutic approaches to prevention and treatment of GVHD. Drugs 2002; 62: 879–89

    Article  PubMed  CAS  Google Scholar 

  15. Nashan B, Moore R, Amlot P, et al. Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients: CHIB 201 International Study Group. Lancet 1997; 350: 1193–8

    Article  PubMed  CAS  Google Scholar 

  16. Kahan BD, Rajagopalan PR, Hall M. Reduction of the occurrence of acute cellular rejection among renal allograft recipients treated with basiliximab, a chimeric anti-interleukin-2-receptor monoclonal antibody: United States Simulect Renal Study Group. Transplantation 1999; 67: 276–84

    Article  PubMed  CAS  Google Scholar 

  17. Kovarik JM, Kahan BD, Rajagopalan PR, et al. Population pharmacokinetics and exposure-response relationships for basiliximab in kidney transplantation. Transplantation 1999; 68: 1288–94

    Article  PubMed  CAS  Google Scholar 

  18. Kovarik JM, Offner G, Broyer M, et al. A rational dosing algorithm for basiliximab (Simulect) in pediatric renal transplantation based on pharmacokinetic-dynamic evaluations. Transplantation 2002; 74: 966–71

    Article  PubMed  CAS  Google Scholar 

  19. Pascual J, Marcen R, Ortuno J. Anti-interleukin-2 receptor antibodies: basiliximab and daclizumab. Nephrol Dial Transplant 2001; 16: 1756–60

    Article  PubMed  CAS  Google Scholar 

  20. Vincenti F, Pace D, Birnbaum J, et al. Pharmacokinetic and pharmacodynamic studies of one or two doses of daclizumab in renal transplantation. Am J Transplant 2003; 3: 50–2

    Article  PubMed  CAS  Google Scholar 

  21. ter Meulen CG, Riemsdijk-van Overbeeke IC, Hene RJ, et al. Steroid-withdrawal at 3 days after renal transplantation with anti-IL-2 receptor alpha therapy: a prospective randomized multicenter study. Am J Transplant 2004; 4: 803–10

    Article  PubMed  Google Scholar 

  22. ter Meulen CG, Baan CC, Hene RJ, et al. Two doses of daclizumab are sufficient for prolonged interleukin-2Ralfa chain blockade [letter]. Transplantation 2001; 72: 1709–10

    Article  PubMed  Google Scholar 

  23. Stratta RJ, Alloway RR, Lo A, et al. Two-dose daclizumab regimen in simultaneous kidney-pancreas transplant recipients: primary endpoint analysis of a multicenter, randomized study. Transplantation 2003; 75: 1260–6

    Article  PubMed  CAS  Google Scholar 

  24. Koch M, Niemeyer G, Patel I, et al. Pharmacokinetics, pharmacodynamics, and immunodynamics of daclizumab in a two-dose regimen in liver transplantation. Transplantation 2002; 73: 1640–6

    Article  PubMed  CAS  Google Scholar 

  25. Kovarik J, Breidenbach T, Gerbeau C, et al. Disposition and immunodynamics if basiliximab in liver allograft recipients. Clin Pharmacol Ther 1998; 64: 66–72

    Article  PubMed  CAS  Google Scholar 

  26. ter Meulen CG, Goertz JHC, Klasen IS, et al. Decreased renal excretion of soluble interleukin-2 receptor alpha after treatment with daclizumab. Kidney Int 2003; 64: 697–704

    Article  PubMed  Google Scholar 

  27. Kovarik JM, Moore R, Wolf P, et al. Screening for basiliximab exposure-response relationships in renal transplantation. Clin Transplant 1999; 13: 32–8

    Article  PubMed  CAS  Google Scholar 

  28. Keown PA, Balshaw R, Krueger H, et al. Economic analysis of basiliximab in renal transplantation. Transplantation 2001; 71: 1573–9

    Article  PubMed  CAS  Google Scholar 

  29. Walters SJ, Whitfield M, Akehurst RL, et al. Economic implications of the use of basiliximab in addition to triple immunosuppressive therapy in renal allograft recipients. Pharmacoeconomics 2003; 21: 129–38

    Article  PubMed  Google Scholar 

  30. Leonard PA, Woodside KJ, Gugliuzza KK, et al. Safe administration of a humanized murine antibody after anaphylaxis to a chimeric murine antibody. Transplantation 2002; 74: 1697–700

    Article  PubMed  Google Scholar 

  31. Baudouin V, Crusiaux A, Haddad E, et al. Anaphylactic shock caused by immunoglobulin E sensitization after retreatment with the chimeric anti-interleukin-2 receptor monocloncal antibody basiliximab. Transplantation 2003; 76: 459–63

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. Department of Hospital Pharmacy, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands

    Teun van Gelder

  2. Department of Surgery, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands

    Michiel Warlé

  3. Department of Internal Medicine, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands

    Rik G. ter Meulen

Authors
  1. Teun van Gelder
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michiel Warlé
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rik G. ter Meulen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Teun van Gelder.

Rights and permissions

Reprints and permissions

About this article

Cite this article

van Gelder, T., Warlé, M. & ter Meulen, R.G. Anti-Interleukin-2 Receptor Antibodies in Transplantation. Drugs 64, 1737–1741 (2004). https://doi.org/10.2165/00003495-200464160-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200464160-00001

Keywords

Search

Navigation