Costimulation Blockade with Belatacept in Renal Transplantation

Vincenti, Flavio; Larsen, Christian; Dürrbach, Antoine; Wekerle, Thomas; Nashan, Björn; Blancho, Gilles; Lang, Philippe; Grinyó, Josep M.; Halloran, Philip F.; Solez, Kim; Hagerty, David; Levy, Elliott; Zhou, Wangda; Natarajan, Kannan; Charpentier, B

doi:10.1056/nejmoa050085

Cited by 800 publications

(596 citation statements)

References 39 publications

Supporting

Mentioning

576

Contrasting

Unclassified

Order By: Relevance

“…It blocks stimulatory signal between CD28 receptor on T cells and CD80 and CD86 on the antigen presenting cell by simulating CTLA-4 activity (CTLA-4 is negative regulator by competing with CD28 for CD80/86 binding). 45 A recent abstract showed comparable efficacy of Belatacept as compared to Tacrolimus alone (inferior to Tacrolimus and Mycophenolate combination) with fewer metabolic, neurological and renal side effects. 46 …”

Section: Other New Drugsmentioning

confidence: 99%

Current Status of Immunosuppression in Liver Transplantation

Choudhary

Saigal

Shukla

et al. 2013

Journal of Clinical and Experimental Hepatology

View full text Add to dashboard Cite

With advancements in immunosuppressive strategies and availability of better immunosuppressive agents, survival rate following liver transplantation has improved significantly in the recent times. Besides improvements in surgical techniques, the most important factor that has contributed to this better outcome is the progress made in the field of immunosuppression. Over the last several years, the trend has changed to tailored immunosuppression with the aim of achieving optimal graft function while avoiding its undesirable side effects. Induction agents are no longer used routinely and the aim is to provide minimal immunosuppression in the maintenance phase. The present review discusses the various types of immunosuppressive agents, their mechanism of action, clinical utility, advantages and disadvantages, and their side effects in short and long-term. It also discusses about tailoring immunosuppression in presence of various situations such as renal dysfunction, metabolic syndrome, hepatitis C recurrence, cytomegalovirus infections and so on. The issue of chronic kidney disease and the available renal sparing immunosuppressive strategies has been particularly stressed upon. Finally, it discusses about the practical aspects of various immunosuppression regimens including drug monitoring. ( J CLIN EXP HEPATOL 2013;3:150-158)

show abstract

Section: Other New Drugsmentioning

confidence: 99%

Current Status of Immunosuppression in Liver Transplantation

Choudhary

Saigal

Shukla

et al. 2013

Journal of Clinical and Experimental Hepatology

View full text Add to dashboard Cite

show abstract

“…The design of IM103‐100 (NCT00035555) has been described 9. Briefly, IM103‐100 was a 12‐month, open‐label, phase II study of kidney transplant recipients aged ≥18 years.…”

Section: Methodsmentioning

confidence: 99%

“…Belatacept was evaluated as part of a calcineurin inhibitor–free immunosuppressive regimen in the phase II IM103‐100 study, in which patients undergoing renal transplantation were randomized to receive 1 of 2 belatacept‐based dosing regimens or cyclosporine (CsA)‐based immunosuppression 9. While the efficacy of belatacept was comparable with CsA, renal function was significantly better in belatacept‐treated vs CsA‐treated patients at 12 months posttransplant 9. The present post hoc analysis compared outcomes at 10 years posttransplant in belatacept‐treated and CsA‐treated patients participating in IM103‐100.…”

Section: Introductionmentioning

confidence: 99%

Ten-year outcomes in a randomized phase II study of kidney transplant recipients administered belatacept 4-weekly or 8-weekly

Vincenti

Blancho

Dürrbach

et al. 2017

American Journal of Transplantation

View full text Add to dashboard Cite

In the phase II IM103‐100 study, kidney transplant recipients were first randomized to belatacept more‐intensive‐based (n = 74), belatacept less‐intensive‐based (n = 71), or cyclosporine‐based (n = 73) immunosuppression. At 3‐6 months posttransplant, belatacept‐treated patients were re‐randomized to receive belatacept every 4 weeks (4‐weekly, n = 62) or every 8 weeks (8‐weekly, n = 60). Patients initially randomized to cyclosporine continued to receive cyclosporine‐based immunosuppression. Cumulative rates of biopsy‐proven acute rejection (BPAR) from first randomization to year 10 were 22.8%, 37.0%, and 25.8% for belatacept more‐intensive, belatacept less‐intensive, and cyclosporine, respectively (belatacept more‐intensive vs cyclosporine: hazard ratio [HR] = 0.95; 95% confidence interval [CI] 0.47‐1.92; P = .89; belatacept less‐intensive vs cyclosporine: HR = 1.61; 95% CI 0.85‐3.05; P = .15). Cumulative BPAR rates from second randomization to year 10 for belatacept 4‐weekly, belatacept 8‐weekly, and cyclosporine were 11.1%, 21.9%, and 13.9%, respectively (belatacept 4‐weekly vs cyclosporine: HR = 1.06, 95% CI 0.35‐3.17, P = .92; belatacept 8‐weekly vs cyclosporine: HR = 2.00, 95% CI 0.75‐5.35, P = .17). Renal function trends were estimated using a repeated‐measures model. Estimated mean GFR values at year 10 for belatacept 4‐weekly, belatacept 8‐weekly, and cyclosporine were 67.0, 68.7, and 42.7 mL/min per 1.73 m2, respectively (P<.001 for overall treatment effect). Although not statistically significant, rates of BPAR were 2‐fold higher in patients administered belatacept every 8 weeks vs every 4 weeks.

show abstract

“…< costimulation B7-CD28 car il a une affinité trop faible pour B7.2 (CD86). En réponse à ce problème, une molécule analogue à l'abatacept a été créée, le bélatacept (LEA 29Y), qui a deux mutations remplaçantes situées dans les boucles CDR1 (complementary determining regions) de la portion extracellulaire de CTLA-4, ce qui lui confère une avidité quatre fois plus importante pour B7.2 (CD86) et deux fois plus forte pour B7.1 (CD80) [11]. Ainsi, l'exemple de ces deux molécules, l'abatacept et le bélatacept, démontre qu'une stratégie fondée sur les modifications de structure permet d'obtenir la molécule la plus efficace possible dans des situations bien définies avec, si possible, une meilleure tolérance [12].…”

Section: éTanerceptunclassified

Protéine de fusion ou anticorps monoclonal

Sibilia

2009

Med Sci (Paris)

View full text Add to dashboard Cite

Costimulation Blockade with Belatacept in Renal Transplantation

Abstract: Belatacept, an investigational selective costimulation blocker, did not appear to be inferior to cyclosporine as a means of preventing acute rejection after renal transplantation. Belatacept may preserve the glomerular filtration rate and reduce the rate of chronic allograft nephropathy.

Cited by 800 publications

References 39 publications

Current Status of Immunosuppression in Liver Transplantation

Current Status of Immunosuppression in Liver Transplantation

Ten-year outcomes in a randomized phase II study of kidney transplant recipients administered belatacept 4-weekly or 8-weekly

Protéine de fusion ou anticorps monoclonal

Contact Info

Product

Resources

About