Belatacept: A novel biologic for maintenance immunosuppression after renal transplantation

Pharmacotherapy

Volumn 31, Issue 4, 2011, Pages 394-407

  Martin, Spencer T ^a   Tichy, Eric M ^b   Gabardi, Steven ^c  

^a NEW YORK PRESBYTERIAN HOSPITAL   (United States)

^b YALE NEW HAVEN HOSPITAL   (United States)

^c BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

Belatacept; Immunosuppression; Renal transplantation

Indexed keywords

ABATACEPT; AZATHIOPRINE; B7 ANTIGEN; BASILIXIMAB; BELATACEPT; CD28 ANTIGEN; CD86 ANTIGEN; CORTICOSTEROID; CYCLOSPORIN; CYCLOSPORIN A; IMMUNOSUPPRESSIVE AGENT; METHYLPREDNISOLONE; MYCOPHENOLIC ACID; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PREDNISONE; RAPAMYCIN; TACROLIMUS;

ACUTE GRAFT REJECTION; ANEMIA; ANTIGEN ANTIBODY REACTION; BACTERIAL INFECTION; CELLULAR IMMUNITY; CONSTIPATION; CYTOMEGALOVIRUS INFECTION; DIABETES MELLITUS; DIARRHEA; DISORDERS OF CARBOHYDRATE METABOLISM; DRUG BLOOD LEVEL; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG MECHANISM; DRUG POTENCY; DRUG SAFETY; DRUG WITHDRAWAL; EPSTEIN BARR VIRUS; GRAFT FAILURE; GRAFT RECIPIENT; GRAFT SURVIVAL; GRAFT VERSUS HOST REACTION; HUMAN; HYPERTENSION; HYPOKALEMIA; IMMUNOSUPPRESSIVE TREATMENT; KIDNEY ALLOGRAFT REJECTION; KIDNEY DYSFUNCTION; KIDNEY TRANSPLANTATION; LEUKOPENIA; LYMPHOCYTE PROLIFERATION; LYMPHOPROLIFERATIVE DISEASE; MAINTENANCE THERAPY; METABOLIC DISORDER; MOUTH ULCER; MYCOSIS; NAUSEA; NEUROTOXICITY; QUALITY OF LIFE; REVIEW; SKIN TOXICITY; SURVIVAL RATE; SURVIVAL TIME; T LYMPHOCYTE ACTIVATION; TREATMENT DURATION; URINARY TRACT INFECTION; VIRUS INFECTION;

CLINICAL TRIALS AS TOPIC; HUMANS; IMMUNOCONJUGATES; IMMUNOSUPPRESSION; IMMUNOSUPPRESSIVE AGENTS; KIDNEY TRANSPLANTATION; TREATMENT OUTCOME;

EID: 79953687090     PISSN: 02770008     EISSN: None     Source Type: Journal    
DOI: 10.1592/phco.31.4.394     Document Type: Review

References (81)

1. Pirsch JD, Ploeg RJ, Gange S, et al. Determinants of graft survival after renal transplantation. Transplantation 1996;61:1581-6. (Pubitemid 26190899)
2. Humar A, Ramcharan T, Kandaswamy R, Gillingham K, Payne WD, Matas AJ. Risk factors for slow graft function after kidney transplants: a multivariate analysis. Clin Transplant 2002;16:425-9. (Pubitemid 36004274)
3. Flechner SM, Modlin CS, Serrano DP, et al. Determinants of chronic renal allograft rejection in cyclosporine-treated recipients. Transplantation 1996;62:1235-41.
4. Vadivel N, Tullius SG, Chandraker A. Chronic allograft nephropathy. Semin Nephrol 2007;27:414-29. (Pubitemid 47002069)
5. Tesi RJ, Elkhammas EA, Henry ML, Davies EA, Salazar A, Ferguson RM. Acute rejection episodes: best predictor of long-term primary cadaveric renal transplant survival. Transplant Proc 1993;25:901-2. (Pubitemid 23078829)
6. Almond PS, Matas A, Gillingham K, et al. Risk factors for chronic rejection in renal allograft recipients. Transplantation 1993;55:752-6, discussion 6-7.
7. Ferguson R. Acute rejection episodes: best predictor of long-term primary cadaveric renal transplant survival. Clin Transplant 1994;8:328-31. (Pubitemid 24163500)
8. Hariharan S, Johnson CP, Bresnahan BA, Taranto SE, McIntosh MJ, Stablein D. Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Engl J Med 2000;342:605-12.
9. Gaston RS. Current and evolving immunosuppressive regimens in kidney transplantation. Am J Kidney Dis 2006;47:S3-21.
10. First MR. Improving long-term renal transplant outcomes with tacrolimus: speculation vs evidence. Nephrol Dial Transplant 2004;19(suppl 6):vi17-22.
11. Kaplan B, Schold JD, Meier-Kriesche HU. Long-term graft survival with Neoral and tacrolimus: a paired kidney analysis. J Am Soc Nephrol 2003;14:2980-4. (Pubitemid 37305662)
12. Kramer BK, Montagnino G, Del Castillo D, et al. Efficacy and safety of tacrolimus compared with cyclosporin A microemulsion in renal transplantation: 2-year follow-up results. Nephrol Dial Transplant 2005;20:968-73. (Pubitemid 40704035)
13. Vincenti F, Jensik SC, Filo RS, et al. A long-term comparison of tacrolimus (FK506) and cyclosporine in kidney transplantation: evidence for improved allograft survival at five years. Transplantation 2002;73:775-82. (Pubitemid 34260577)
14. Boots JM, Christiaans MH, van Hooff JP. Effect of immunosuppressive agents on long-term survival of renal transplant recipients: focus on the cardiovascular risk. Drugs 2004;64:2047-73. (Pubitemid 39280373)
15. Trompeter R, Filler G, Webb NJ, et al. Randomized trial of tacrolimus versus cyclosporin microemulsion in renal transplantation. Pediatr Nephrol 2002;17:141-9. (Pubitemid 36076024)
16. Artz MA, Boots JM, Ligtenberg G, et al. Improved cardiovascular risk profile and renal function in renal transplant patients after randomized conversion from cyclosporine to tacrolimus. J Am Soc Nephrol 2003;14:1880-8. (Pubitemid 36750484)
17. Shihab FS, Waid TH, Conti DJ, et al. Conversion from cyclosporine to tacrolimus in patients at risk for chronic renal allograft failure: 60-month results of the CRAF study. Transplantation 2008;85:1261-9. (Pubitemid 351670474)
18. Meier-Kriesche HU, Schold JD, Srinivas TR, Kaplan B. Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am J Transplant 2004;4:378-83. (Pubitemid 38282293)
19. Flechner SM, Kobashigawa J, Klintmalm G. Calcineurin inhibitor-sparing regimens in solid organ transplantation: focus on improving renal function and nephrotoxicity. Clin Transplant 2008;22:1-15. (Pubitemid 351149996)
20. Pascual J, Zamora J, Galeano C, Royuela A, Quereda C. Steroid avoidance or withdrawal for kidney transplant recipients. Cochrane Database Syst Rev 2009;(1):CD005632.
21. Kreis H, Cisterne JM, Land W, et al. Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients. Transplantation 2000;69:1252-60. (Pubitemid 30238708)
22. Johnson RW, Kreis H, Oberbauer R, Brattstrom C, Claesson K, Eris J. Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure. Transplantation 2001;72:777-86. (Pubitemid 32879845)
23. Oberbauer R, Kreis H, Johnson RW, et al. Long-term improvement in renal function with sirolimus after early cyclosporine withdrawal in renal transplant recipients: 2-year results of the Rapamune maintenance regimen study. Transplantation 2003;76:364-70. (Pubitemid 36928000)
24. Oberbauer R, Segoloni G, Campistol JM, et al. Early cyclosporine withdrawal from a sirolimus-based regimen results in better renal allograft survival and renal function at 48 months after transplantation. Transpl Int 2005;18:22-8. (Pubitemid 41742941)
25. Ekberg H, Tedesco-Silva H, Demirbas A, et al, for the ELITE-Symphony Study. Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med 2007;357:2562-75. (Pubitemid 350294223)
26. Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med 2004;351:2715-29. (Pubitemid 39665325)
27. Vincenti F, Luggen M. T cell costimulation: a rational target in the therapeutic armamentarium for autoimmune diseases and transplantation. Annu Rev Med 2007;58:347-58. (Pubitemid 46706519)
28. Anderson DE, Sharpe AH, Hafler DA. The B7-CD28/CTLA-4 costimulatory pathways in autoimmune disease of the central nervous system. Curr Opin Immunol 1999;11:677-83.
29. Sayegh MH, Turka LA. The role of T-cell costimulatory activation pathways in transplant rejection. N Engl J Med 1998;338:1813-21.
30. Wang D, Matsumoto R, You Y, et al. CD3/CD28 costimulation-induced NF-kappaB activation is mediated by recruitment of protein kinase C-theta, Bcl10, and IkappaB kinase beta to the immunological synapse through CARMA1. Mol Cell Biol 2004;24:164-71.
31. McAdam AJ, Schweitzer AN, Sharpe AH. The role of B7 costimulation in activation and differentiation of CD4+ and CD8+ T cells. Immunol Rev 1998;165:231-47. (Pubitemid 28524215)
32. Alegre ML, Frauwirth KA, Thompson CB. T-cell regulation by CD28 and CTLA-4. Nat Rev Immunol 2001;1:220-8. (Pubitemid 33741960)
33. Schwartz RH. A cell culture model for T lymphocyte clonal anergy. Science 1990;248:1349-56.
34. Pentcheva-Hoang T, Egen JG, Wojnoonski K, Allison JP. B7-1 and B7-2 selectively recruit CTLA-4 and CD28 to the immunological synapse. Immunity 2004;21:401-13. (Pubitemid 39208341)
35. Abrams JR, Lebwohl MG, Guzzo CA, et al. CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris. J Clin Invest 1999;103:1243-52.
36. Kremer JM, Westhovens R, Leon M, et al. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N Engl J Med 2003;349:1907-15. (Pubitemid 37409707)
37. Genovese MC, Becker JC, Schiff M, et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med 2005;353:1114-23. (Pubitemid 41317434)
38. Kremer JM, Dougados M, Emery P, et al. Treatment of rheumatoid arthritis with the selective costimulation modulator abatacept: 12-month results of a phase IIb, double-blind, randomized, placebo-controlled trial. Arthritis Rheum 2005;52:2263-71. (Pubitemid 41117408)
39. Kremer JM, Genant HK, Moreland LW, et al. Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. Ann Intern Med 2006;144:865-76. (Pubitemid 46768126)
40. Weisman MH, Durez P, Hallegua D, et al. Reduction of inflammatory biomarker response by abatacept in treatment of rheumatoid arthritis. J Rheumatol 2006;33:2162-6. (Pubitemid 44749773)
41. Turka LA, Linsley PS, Lin H, et al. T-cell activation by the CD28 ligand B7 is required for cardiac allograft rejection in vivo. Proc Natl Acad Sci U S A 1992;89:11102-5.
42. Lenschow DJ, Zeng Y, Thistlethwaite JR, et al. Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4lg. Science 1992;257:789-92.
43. Larsen CP, Pearson TC, Adams AB, et al. Rational development of LEA29Y (belatacept), a high-affinity variant of CTLA4-Ig with potent immunosuppressive properties. Am J Transplant 2005;5:443-53. (Pubitemid 40313335)
44. Greene JL, Leytze GM, Emswiler J, et al. Covalent dimerization of CD28/CTLA-4 and oligomerization of CD80/CD86 regulate T cell costimulatory interactions. J Biol Chem 1996;271:26762-71. (Pubitemid 26359085)
45. Linsley PS, Greene JL, Brady W, Bajorath J, Ledbetter JA, Peach R. Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity 1994;1:793-801.
46. Latek R, Fleener C, Lamian V, et al. Assessment of belatacept-mediated costimulation blockade through evaluation of CD80/86-receptor saturation. Transplantation 2009;87:926-33.
47. Vincenti F, Charpentier B, Vanrenterghem Y, et al. A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study). Am J Transplant 2010;10:535-46.
48. Vincenti F, Larsen C, Durrbach A, et al. Costimulation blockade with belatacept in renal transplantation. N Engl J Med 2005;353:770-81. (Pubitemid 41215486)
49. Durrbach A, Pestana JM, Pearson T, et al. A phase III study of belatacept versus cyclosporine in kidney transplants from extended criteria donors (BENEFIT-EXT study). Am J Transplant 2010;10:547-57.
50. Gandhi AM, Fazli U, Rodina V, Qazi YA. Costimulation targeting therapies in organ transplantation. Curr Opin Organ Transplant 2008;13:622-6.
51. Zhou Z, Shen J, Kaul S, Pfister M, Roy A. Belatacept population pharmacokinetics in renal transplant patients [abstract 1505]. Presented at the American transplant congress, San Diego, CA, May 2-5, 2010.
52. Ferguson R, Vincenti F, Kaufman DB, et al. Immunosuppression with belatacept-based, CNI-avoiding and steroid-avoiding regimens vs a tacrolimus-based, steroid-avoiding regimen in kidney transplant patients: results of a 1-year, randomized study [abstract 372]. Presented at the American transplant congress, San Diego, CA, May 2-5, 2010.
53. Larsen CP, Grinyo J, Charpentier B, et al. Belatacept vs cyclosporine in kidney transplant recipients: 2-year outcomes from the BENEFIT study [abstract 142]. Presented at the American transplant congress, San Diego, CA, May 2-5, 2010.
54. Vincenti F, Blancho G, Durrbach A, et al. Five-year safety and efficacy of belatacept in renal transplantation. J Am Soc Nephrol 2010;21:1587-96.
55. Rostaing L, Nainan G, del C Rial M, et al. Switch from a CNI-to a belatacept-based immunosuppressive regimen in kidney transplant recipients is safe and results in better renal function: 12-month results from a phase II study [abstract 166]. Presented at the American transplant congress, San Diego, CA, May 2-5, 2010.
56. U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients. 2004 annual report: transplant data 1994-2003. Rockville, MD: Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation; Richmond, VA: United Network for Organ Sharing; Ann Arbor, MI: University Renal Research and Education Association.
57. Metzger RA, Delmonico FL, Feng S, Port FK, Wynn JJ, Merion RM. Expanded criteria donors for kidney transplantation. Am J Transplant 2003;3(suppl 4):114-25. (Pubitemid 36612389)
58. Caillard S, Dharnidharka V, Agodoa L, Bohen E, Abbott K. Posttransplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression. Transplantation 2005;80:1233-43. (Pubitemid 41746802)
59. Faull RJ, Hollett P, McDonald SP. Lymphoproliferative disease after renal transplantation in Australia and New Zealand. Transplantation 2005;80:193-7. (Pubitemid 41061675)
60. Libertiny G, Watson CJ, Gray DW, Welsh KI, Morris PJ. Rising incidence of post-transplant lymphoproliferative disease in kidney transplant recipients. Br J Surg 2001;88:1330-4. (Pubitemid 32955411)
61. Cavaliere R, Petroni G, Lopes MB, et al. Primary central nervous system post-transplantation lymphoproliferative disorder: an international primary centeral nervous system lymphoma collaborative group report. Cancer 2010;116:863-70.
62. Dharnidharka VR. Costimulation blockade with belatacept in renal transplantation. N Engl J Med 2005;353:2085-6. (Pubitemid 41609106)
63. Schiff J, Cole E, Cantarovich M. Therapeutic monitoring of calcineurin inhibitors for the nephrologist. Clin J Am Soc Nephrol 2007;2:374-84.
64. Sommerer C, Giese T, Meuer S, Zeier M. Pharmacodynamic monitoring of calcineurin inhibitor therapy: is there a clinical benefit? Nephrol Dial Transplant 2009;24:21-7.
65. Wavamunno MD, Chapman JR. Individualization of immunosuppression: concepts and rationale. Curr Opin Organ Transplant 2008;13:604-8.
66. Yano I. Pharmacodynamic monitoring of calcineurin phosphatase activity in transplant patients treated with calcineurin inhibitors. Drug Metab Pharmacokinet 2008;23:150-7.
67. Holt DW. Therapeutic drug monitoring of immunosuppressive drugs in kidney transplantation. Curr Opin Nephrol Hypertens 2002;11:657-63. (Pubitemid 35440849)
68. de Jonge H, Naesens M, Kuypers DR. New insights into the pharmacokinetics and pharmacodynamics of the calcineurin inhibitors and mycophenolic acid: possible consequences for therapeutic drug monitoring in solid organ transplantation. Ther Drug Monit 2009;31:416-35.
69. Budde K, Glander P. Pharmacokinetic principles of immunosuppressive drugs. Ann Transplant 2008;13:5-10.
70. Masuda S, Inui K. An up-date review on individualized dosage adjustment of calcineurin inhibitors in organ transplant patients. Pharmacol Ther 2006;112:184-98. (Pubitemid 44301492)
71. Kuypers DR. Influence of interactions between immunosuppressive drugs on therapeutic drug monitoring. Ann Transplant 2008;13:11-18.
72. Burkhart C, Heusser C, Morris RE, et al. Pharmacodynamics in the development of new immunosuppressive drugs. Ther Drug Monit 2004;26:588-92. (Pubitemid 39579138)
73. Schweizer RT, Rovelli M, Palmeri D, Vossler E, Hull D, Bartus S. Noncompliance in organ transplant recipients. Transplantation 1990;49:374-7. (Pubitemid 20088179)
74. Bunzel B, Laederach-Hofmann K. Solid organ transplantation: are there predictors for posttransplant noncompliance? A literature overview. Transplantation 2000;70:711-16.
75. De Geest S, Borgermans L, Gemoets H, et al. Incidence, determinants, and consequences of subclinical noncompliance with immunosuppressive therapy in renal transplant recipients. Transplantation 1995;59:340-7.
76. Didlake RH, Dreyfus K, Kerman RH, Van Buren CT, Kahan BD. Patient noncompliance: a major cause of late graft failure in cyclosporine-treated renal transplants. Transplant Proc 1998;20:63-9.
77. Vasquez EM, Tanzi M, Benedetti E, Pollak R. Medication noncompliance after kidney transplantation. Am J Health Syst Pharm 2003;60:266-9. (Pubitemid 36749051)
78. Kiley DJ, Lam CS, Pollak R. A study of treatment compliance following kidney transplantation. Transplantation 1993;55:51-6. (Pubitemid 23033944)
79. Chisholm MA, Mulloy LL, DiPiro JT. Comparing renal transplant patients' adherence to free cyclosporine and free tacrolimus immunosuppressant therapy. Clin Transplant 2005;19:77-82. (Pubitemid 40227856)
80. Ashman N, Chapagain A, Dobbie H, Raftery MJ, Sheaff MT, Yaqoob MM. Belatacept as maintenance immunosuppression for postrenal transplant de novo drug-induced thrombotic microangiopathy. Am J Transplant 2009;9:424-7.
81. Midtvedt K, Bitter J, Dørje C, Stenstrøm J, Bjørneklett R, Holdaas H. Belatacept as rescue treatment for recurrence of haemolytic-uremic syndrome after renal transplantation [abstract 766]. Presented at the American transplant congress, Boston, MA, May 30-June 3, 2009.