Clinical Immunology Society

Basiliximab

Compound Name:BasiliximabMolecular Target:CD25 (IL-2Ra)Molecular Structure:chimeric monoclonal antibody IgG1κLicensed Indication:Prophylaxis of acute organ rejection in adults following cadaveric- or living-donor renal transplantation as part of an immunosuppressive regimen including cyclosporine and corticosteroidsManufacturer and/or Distributor:NovartisInitial FDA Approval:1998Summary:

Basiliximab is a chimeric (murine/human) monoclonal antibody (IgG1k) that functions as an immunosuppressive agent via specifically binding to and blocking the high affinity subunit of the interleukin-2 receptor, also known as CD25 or IL2Rα. The expression of this receptor chain is induced on the surface of T lymphocytes upon antigenic activation and regulatory T cells express it constitutively. The specific and high-affinity binding of basiliximab to IL2Rα competitively inhibits IL2-mediated activation of lymphocytes, thereby dampening T cell-mediated allograft rejection.

 

Basiliximab is indicated for the prophylaxis of acute organ rejection in renal transplant patients. In a recent open-label, multi-center randomized control trial (Harmony), the efficacy of rabbit ATG and basiliximab induction regimens were studied in renal transplant patients undergoing rapid steroid withdrawal. Basiliximab was non-inferior to rabbit ATG for preventing biopsy-proven acute rejection one year after transplantation in patients that had rapid withdrawal of steroids. A recent meta-analysis examined the use of basiliximab and daclizumab for the prevention of hepatic graft rejection in adults and showed that although both drugs lower rates of acute rejection, mortality is not reduced. Moreover the subgroup analyses indicated no significant differences in acute rejection and mortality rates when comparing use of IL2Rα blockade to that of steroids. As such, basiliximab may also be used for acute rejection in liver transplant patients. Finally, a European regulatory review that investigated the safety and efficacy of basiliximab for off-label use in heart transplantation found no adequately powered randomized studies in heart transplantation and included a new warning in the product information regarding the lack of proven safety in heart transplantation.

 

The first dose for adults (20 mg) and children (10 mg) is given within 2 h before the transplant surgery, followed by the second dose 4 days after transplantation

 

Adverse effects include:

  1. post-administration anaphylaxis, for which the FDA warning advisory was issued in 2000;
  2. cardiovascular (hypertension, hypotension, angina pectoris, arrhythmia, tachycardia);
  3. respiratory (dyspnea, respiratory tract infection, rhinitis, bronchitis, pulmonary edema);
  4. hematologic (anemia, thrombocytopenia, thrombosis, purpura);
  5. dermatologic (acne, herpes simplex, herpes zoster, skin ulceration);
  6. others, including dizziness, fatigue, malaise, abdominal pain. Infectious complications are frequently seen in the immunosuppressed population treated with basiliximab.

 

A black box warning indicates that the drug should only be used by physicians with appropriate experience in transplantation and immunosuppression.

References

Package Insert

 

  1. 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 Jan 27;67(2):276-284. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1007559
  2. Nashan B, Moore R, Amlot P, Schmidt AG, Abeywickrama K, Soulillou JP. Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group. Lancet. 1997 Oct 25;350(9086):1193-1198. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9652559
  3. McKeage K, McCormack PL. Basiliximab: a review of its use as induction therapy in renal transplantation. BioDrugs. 2010 Feb 1;24(1):55-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20055533
  4. Penninga LMøller CHGustafsson FGluud CSteinbrüchel DA. Immunosuppressive T-cell antibody induction for heart transplant recipients. Cochrane Database Syst Rev. 2013 Dec 2;12:CD008842. http://www.ncbi.nlm.nih.gov/pubmed/24297433
  5. Lee SDKim SHKong SYKim YKPark SJ. Kinetics of B, T, NK lymphocytes and isoagglutinin titers in ABO incompatible living donor liver transplantation using rituximab and basiliximab. Transpl Immunol. 2014 Nov 20. http://www.ncbi.nlm.nih.gov/pubmed/25449537
  6. Ansari D, Höglund P, Andersson B, Nilsson J. Comparison of Basiliximab and Anti-Thymocyte Globulin as Induction Therapy in Pediatric Heart Transplantation: A Survival Analysis. J Am Heart Assoc. 2015 Dec 31;5(1). http://www.ncbi.nlm.nih.gov/pubmed/26722127
  7. Zhang y, Jin W, Cai X. Anti-interleukin-2 receptor antibodies for the prevention of rejection in liver transplant recipients: a systematic review and meta-analysis. Ann Med 2016 Nov 4:1-33. https://www.ncbi.nlm.nih.gov/pubmed/27813419
  8. Thomusch OWiesener MOpgenoorth MPascher AWoitas RPWitzke OJaenigen BRentsch MWolters HRath TCingöz TBenck UBanas BHugo C. Rabbit-ATG or basiliximab induction for rapid steroid withdrawal after renal transplantation (Harmony): an open-label, multicentre, randomised controlled trial. Lancet. 2016 Dec 17;388(10063):3006-3016. https://www.ncbi.nlm.nih.gov/pubmed/27871759
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