Costimulation Blockade with Belatacept in Renal Transplantation This is another study for the previous authors. Please summarize the conclusion of both studies. Suggest a role of belatacept in the management of renal transplantation.
Belatacept is selective costimulatory blockade agent that inhibit T cell activation at CD28- CD80 -CD86 pathway.
This study randomized partially blinded multicenter phase 11 trial to assess the efficacy of belatacept with CNI withdraw in preventing acute rejection at 6 months as primary objective and secondary objective was to assess its effect on graft and patient survival at 12 months, also assess the rate of Chronic allograft nephropathy and other metabolic risk like cardiovascular event, HTN and dyslipidemia
They divided the patients in to three groups 1.1.1 the more intense belatacept group, low intense belatacept group and cyclosporine group, all received induction with basiliximab ( IL2 inhibitors ) followed by MPA and steroid ,this study conclude that the belatacept in both intense and low dose was noninferiority than cyclosporine in prevention of acute rejection at first 6 months and better measured GFR in both belatacept group than cyclosporine but similar impact on graft and patient survival at 12 months with lower incidence of CAN in both belatacept arms and less metabolic complication like dyslipidemia and HTN compared to cyclosporine group
Belatacept its promising immunosuppressive agent that can be used with CNI avoidance or CNI minimization or sparing protocol but preferred to be compared with the more potent CNI agent like tacrolimus as its now consider standard maintenance therapy with proven efficacy in lowering the acute rejection rate compared to cyclosporine .
AMAL Anan
3 years ago
Belatacept represents a new class of primary
immunosuppressants, arguably the first since the
introduction of cyclosporine, the first calcineurin
inhibitor. Whereas calcineurin inhibitors block or
diminish the effects of T-cell activation on allografts, belatacept prevents T-cell activation.
accomplished without concurrent global immunosuppression of T-cell–depletion strategies. Our results suggest that belatacept can provide a level of
immunosuppressive efficacy in renal-transplant
recipients similar to that afforded by cyclosporine,
but with the potential benefits of improved cardiovascular and metabolic risk profiles, greater preservation of kidney function, and a lower incidence of chronic allograft nephropathy
Suggest a role of belatacept in the management of renal transplantation.
Kidney transplant, prophylaxis of organ rejection: IV: Note: Use in combination with basiliximab induction, mycophenolate mofetil, and corticosteroids.
Initial phase: 10 mg/kg on day 1 (day of transplant, prior to implantation) and on day 5 (~96 hours after day 1 dose), followed by 10 mg/kg at the end of week 2, week 4, week 8, and week 12 following transplantation
Maintenance phase: 5 mg/kg every 4 weeks (plus or minus 3 days) beginning at the end of week 16 following transplantation
References
Combs J, Kagan A, Boelkins M, Coscia L, Moritz M, Hofmann RM. Belatacept during pregnancy in renal transplant recipients: two case reports. Am J Transplant. 2018;18(8):2079-2082. doi:10.1111/ajt.14911 [PubMed 29719109]
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(3):547-57. [PubMed 20415898]
Enderby CY, Habib P, Patel PC, Yip DS, Orum S, Hosenpud JD. Belatacept maintenance in a heart transplant recipient. Transplantation. 2014;98(7):e74-75. [PubMed 25285956]
Ibrahim Omar
3 years ago
1- This is another study for the previous authors. Please summarise the conclusion of both studies.
Belatacept is a promising immunosuppressive medicine in the field of transplantation. its mechanism of action is a selective blocker of T-cell activation. by blocking CD80 and CD86 receptors on antigen presenting cells. so, it inhbits their interaction with CD28 on T-lymphocytes. both CD80 and CD28 are reponsible for co-stimulation. it is less toxic than CNIs and has almost similar efficacy.
this study was done for comparing its effect with cyclosporine. it was evaluated with 2 regimens (intensive and less intensive Belatacept) in comparision to cyclosporine.
the results were favourable for the use of Belatacept instead of CNIs owing to the following :
1- the incidence of acute rejection, in the 1st 6 months, was similar to Cyclopsorine.
2- eGFR was even higher at 1 year post-transplantation with Belatacept.
3- the incidence of chronic allograft nephropathy was lower with using Belatacept as compared to CNIs.
4- the incidence of dyslipidemia and hypertension was almost similar to that of cyclosporine.
2- Suggest a role of belatacept in the management of renal transplantation.
it can be used as CNI sparing agent and can be tried in some selected patients pending larger studies.
Nasrin Esfandiar
3 years ago
Q1: This study showed that belatacept is non- inferior to cyclosporine in terms of acute rejection at six months. Belatacept was better than cyclosporine in regard to one year GFR and chronic allograft nephropathy. Eventually belatacept was slightly better than cyclosporine in lipid or blood pressure levels. Previous study showed no difference between patients and graft survival or one year renal function between groups. Lower cardiovascular or metabolic adverse effects but more acute rejection rates during first year were seen in belatacept group. Both showed safety of belatacept as a new immunosuppressant drug. Q2: Belatacept is considered as a CNI –sparing immunosuppressant protocol to reduce nephrotoxicity of CNIs .Also, non – adherent patients could be considered for this treatment because of 4-6weeks injection intervals for belatacept. This could be in form of CNI avoidance, CNI -minimization or CNI – conversion protocols.
Wessam Moustafa
3 years ago
This study involved 218 patients divided into 3 treatment groups receiving belatacept intense dose , low dose and cyclosporin.
They estimated the incidence of acute rejection 6 month post transplant in the 3 groups and they found it s similar in the 3 groups making belatacept non inferior to cyclosporin as regards incidence of acute rejection, more over the beleatacept groups maintained higher GFR than cyclosporin group .
They concluded that belatacept could perform the same as cyclosporin regarding preventing acute rejections, with the benefit that less cardiovascular side effects .
The previous study concluded that belatacept treated patients was same as cyclosporin regarding patient and graft survival ,
Better regarding occurrence of renal impairment,
And inferior to cyclosporin regarding incidence of acute rejection.
Role of belatacept in transplant patients is to provide same degree of immunosuppression as cyclosporine without the CNI associated side effects.
Last edited 3 years ago by Wessam Moustafa
Reem Younis
3 years ago
Conclusion:-Belatacept, a selective costimulation blocker, binds surface costimulatory ligands (CD80 and CD86) of antigen-presenting cells. Belatacept and cyclosporine had a similar rate of acute rejection, infections, and malignancy.
Belatacept may allow patients to avoid the adverse renal, cardiovascular, and metabolic effects of cyclosporine. The measured glomerular filtration rate at one year was higher among recipients of belatacept than among cyclosporine recipients. Belatacept reduces cholesterol and Blood pressure than cyclosporine. a role of belatacept in the management of renal transplantation :
Belatacept can provide a level of immunosuppressive efficacy in renal-transplant recipients similar to that afforded by cyclosporine, but with the potential benefits of improved cardiovascular and metabolic risk profiles, greater preservation of kidney function, and a lower incidence of chronic allograft nephropathy.
Ben Lomatayo
3 years ago
Conclusion of both studies ; Belatacept is selective co-stimulation blocker, associated with better renal function & less chronic allograft nephropathy, better metabolic and cardiac profile, similar to cyclosporine regarding patients & graft survival at 12 months , more rejection rates was associated with belatacept. Main problems are acute infusion related reaction & PTLD.
Role of Belatacept in renal transplants ; The main idea behind introduction of Belatacept is that being selective co-stimulation blocker, not associated with renal & non-renal sides that is seen with calcineurin inhibitors, and therefore improve cardiovascular status, less incidence of chronic allograft nephropathy , both factors are important causes of mortality in transplant patients.
Theepa Mariamutu
3 years ago
This is another study for the previous authors. Please summarise the conclusion of both studies.
Costimulation Blockade with Belatacept in Renal Transplantation (2005)
This was non-inferiority trial which compared short-term effects of belatacept based regimens as compared to cyclosporine-based regimen on graft function and acute rejection whilst evaluating the cardiovascular and metabolic effects of the both drugs . Belatacept was shown non-inferior to cyclosporine in preventing acute rejection, with better graft function with less rates of chronic allograft nephropathy and less effects cardiovascular and metabolic profile.
A Phase III Study of Belatacept-based Immunosuppression Regimens versus Cyclosporine in Renal Transplant Recipients (BENEFIT Study) (2010)
GTiral evaluated participants 12 months post-transplant which showed belatacept treated patients had better GFR, less chronic allograft nephropathy but similar patient, and graft survival compred to CyA treated group. The belatacept group ad better blood pressure and lipid control. The study concluded that belatacept based immunosuppression regimen is safe and effective in kidney transplants : patient and graft survival, cardiovascular and metabolic profile despite of increased risk of acute rejections.
2. Suggest a role of belatacept in the management of renal transplantation.
Belatacept has role in CNI avoidance therapy for those who has adverse effect or metabolic complications of CNIs.
Shereen Yousef
3 years ago
Costimulation Blockade with Belatacept in Renal Transplantation
The primary objective of this study was to demonstrate the noninferiority of belatacept over cyclosporine with respect to the incidence of acute rejection at six months results suggest that the two agents are similarly effective for the prevention of acute rejection.
Patients treated with belatacept regimens had rates of acute rejection similar to those among patients taking cyclosporine.
subclinical rejection occured with less intensive regimen didn’t affect graft survival or increased the risk of chronic allograft nephropathy.
In this study it was suggested that use of belatacept was superior to cyclosporine as regards the adverse renal, cardiovascular, and metabolic effects of cyclosporine.
The measured GFR at one year was approximately 9 to 13 ml per minute higher among recipients of belatacept than among cyclosporine recipients.
Since the GFR generally declines by approximately 3 ml per minute per 1.73 m2 per year in transplant recipients, these differences, if sustained, could result in improved allograft survival of three to four years.
They also found similar rate of infections and cancer among the groups and PTLD occurred mainly patients with predisposing risk factors to PTLDS (primary Epstein–Barr virus infection or treatment with muromonab-CD3)
In the previous study the authors concluded, that the incidence of acute rejection was higher in the recipients of Belatacept.
The prevalence of biopsy-proven chronic allograft nephropathy at month 12 was lower in the belatacept groups
And PTLD was higher in belatacept group .
And the both studies showed the same results on better effect of balatacept over cyclosporine in metabolic , cardiovascular risk and lipid profile
Suggest a role of belatacept in the management of renal transplantation.
Belatacept can provide a level of immunosuppressive efficacy in renal-transplant recipients similar cyclosporine, with less cardiovascular and metabolic risk profiles and greater preservation of kidney function, a lower incidence of chronic allograft nephropathy and comparable adverse events such as infection and cancer.
Nadia Ibrahim
3 years ago
This is another study for the previous authors. Please summarise the conclusion of both studies. A total of 218 patients were enrolled in this study undergoing kidney transplantation of standard risk . randomly divided into 3 groups, to compare the effect of intensive and low intensive Balatacept Vs cyclosporins mentainence regimens. For one year follow duration At six months, the incidence of acute rejection was similar among the . At 12 months, the glomerular filtration rate was significantly higher with both intensive and less-intensive belatacept than it was with cyclosporine chronic allograft nephropathy was less common with both regimens of belatacept than with cyclosporine Both studies concluded that Balatacept , a selective T cell inactivator (selective costimulation blocker) when used in menaintenance immune suppression among standerd risk recipients didn’t show inferiority to cyclosporine as egard prevention of graft rejection within the first 6 momnths post trnsplantation On the other hand shows superiority over cyclosporins as regard preservation of graft function with less declining rates in GFR in one year post Tx, less incidence of chronic transplant glomerulopathy. Most importantly Belatacept showed improved cardiovascular/metabolic risk profile than Cyclosporins , belatacept was generally safe, although there was a higher incidence of PTLD but were mostly among patients with predisposing risk factors to PTLDS (primary Epstein–Barr virus infection or treatment with muromonab-CD3) (1), and was related to the levels of immunosuppression.(2)
Balatacept was safe to use , no clinical significant difference in incidence of infection compared to cyclosporine, no recorded sever reactions related to infusion. However patients show better metabolic profile , lipid levels, BP levels incidence of NOPTD than cyclosporin Suggest a role of belatacept in the management of renal transplantation. Standerd risk transplant reciepientspreferred to be mentained on Cyclosporin sparing immunesuppression mentainenca regimens prone to cardiovascular , cerebrovascular dyslipdemia, or other metabolic derangements. To prevent CNIs adverse effects. References: (1). Walker RC, Paya CV, Marshall WF, et al. Pretransplantation seronegative Epstein-Barr virus status is the primary risk factor for posttransplantation lymphoproliferative disorder in adult heart, lung, and other solid organ transplantations. J Heart Lung Transplant 1995;14:214-21.
(2). Herzig KA, Juffs HG, Norris D, et al. A single-centre experience of post-renal transplant lymphoproliferative disorder. Transpl Int 2003;16:529-36.
Jamila Elamouri
3 years ago
Costimulation Blockade with Belatacept in Renal Transplantation
Summarize the conclusion
Belatacept is not inferior to cyclosporine in view of preventing acute rejection after kidney transplantation. it maintains the glomerular filtration rate and decreases the rate of chronic allograft nephropathy. The study suggests that the belatacept and cyclosporine has a similar effect in the prevention of acute rejection. With the use of belatacept, the patients may avoid the adverse effect of cyclosporine (renal, cardiovascular, and metabolic). The GFR at one year was about 9 to 13 ml per minute higher among recipients on belatacept than those on cyclosporine. As belatacept is a non-nephrotoxic drug Serum cholesterol levels and blood pressure were similar or slightly lower in the belatacept recipients than in cyclosporine recipients in spite of their use of the lipid-lowering drugs as well, the antihypertensive drugs. Belatacept has the same incidence of cancer as the cyclosporine length and intensity of the immunosuppressive drugs contribute to this risk, and a similar rate of infection as well. In recipients receiving less-intensive therapy, subclinical rejection did not appear to have an adverse effect on graft survival or the risk of chronic allograft nephropathy. The author comment that the difference between belatacept and cyclosporine therapy should be regarded as suggestive rather than definitive. Suggest a role of belatacept in the management of renal transplantation. The study suggests that belatacept can lead to a level of immunosuppressive efficacy similar to that achieved by the cyclosporine, and with potential benefits on cardiovascular and metabolic profiles, greater maintenance of renal function, and a lower incidence of chronic allograft nephropathy.
Mohammed Sobair
3 years ago
1. This is another study for the previous authors. Please summaries the
conclusion of both studies.
Maintenance immunosuppression with CNI yields excellent one-year survival, it is
associated over the long term with high rates of death and graft loss, owing in part to the
adverse renal, cardiovascular, and metabolic effects of these agents.
Use of Belatacept cell blocker which less toxic, may preserve the glomerular filtration
rate and reduce the rate of chronic allograft nephropathy.
In BENEFIT, one of the largest studies in kidney allograft recipients, belatacept was
associated with similar patient and graft survival, superior renal function, a trend toward
less chronic allograft nephropathy and an improved cardiovascular and metabolic profile
compared with cyclosporine 1 year post transplant.
2-Suggest a role of belatacept in the management of renal transplantation.
Belatacept can provide a level of immunosuppressive efficacy in renal-transplant
recipients similar to that afforded by cyclosporine, but with the potential benefits of
improved cardiovascular and metabolic risk profiles, greater preservation of kidney
function, and a lower incidence of chronic allograft nephropathy.
Can be applied in clinical practice if more RCT shows same benefit, especially if
compared to TAC, which more used now and more effective and less toxicity compare to
Cyclosporine.
Mohamed Essmat
3 years ago
Co-stimulation Blockade with Belatacept in Renal Tx This was a non-inferiority trial, comparing short-term effects of belatacept based regimens as compared to cyclosporine based regimen on graft function and graft rejection as well as the cardiovascular and metabolic profile of the patient. The study concluded that belatacept was non-inferior to cyclosporine in preventing acute rejection, with better graft function at end of study period, less rates of CAN. BENEFIT Study A randomized controlled, parallel group, multicenter, Phase III study conducted over 3 years. Aim: To assess effect of Belatacept on graft renal function and its long-term effects vs CNI on. patient and graft survival, acute rejection rates, malignancies and infections. Out of 738 recruited patients, 686 were randomized in 3 groups, namely more intensive (MI), and low intensive (LI) Belatacept regimen and cyclosporine group. Additionally, all were given induction with basiliximab and were on MMF and steroids. At 12 months post-transplant, the study showed that as compared to the cyclosporine group, the belatacept group had better GFR, decreased chronic allograft nephropathy similar patient and graft survival, increased PTLD, with increased rates and grades of acute rejection. Conclusion: As compared to cyclosporine based regimen, Belatacept based immunosuppression regimen is safe and effective in kidney transplants with respect to patient and graft survival having a better graft function, cardiovascular and metabolic profile inspite of increased risk of acute rejections. Suggest a role of belatacept in the management of renal transplantation: the role of belatacept in kidney transplantation is with patients having low risk. It can be used especially in low-risk patients with IHD , Dyslipidemia or metabolic syndrome .
Esmat MD
3 years ago
In the previous study, both Belatacept regimens were associated with better patient and graft survival, superior kidney function, higher incidence of acute rejection episodes, a trend toward less chronic allograft nephropathy and an improved cardiovascular and metabolic profile compared with cyclosporine-based treatment.
This study reported similar results, such as better preservation of GFR, reduced chronic allograft nephropathy in Belatacept groups compared to cyclosporine. The metabolic profile was similar between two groups. In addition, the risk of acute rejection was similar among groups in contrast to previous study (higher incidence of acute rejection in Belatacept groups).
This study showed noninferiority of Belatecept over cyclosporine with respect to the incidence of acute rejection. The frequency of infections and cancers were similar between groups. Cancers including PTLD occur in belatacept groups in a dose dependent fashion and PTLD was associated with EBV infection.
The use of belatacept may allow patients to avoid adverse renal, cardiovascular, and metabolic effects of cyclosporine.
In contrast to cyclosporin which diminishes the effect of T cell activation on graft, belatacept prevents T cell activation. Belatacept can provide a level of immunosuppressive efficacy in renal-transplant recipients similar to that afforded by cyclosporine, but with the potential benefits of improved cardiovascular and metabolic risk profiles, greater preservation of kidney function, a lower incidence of chronic allograft nephropathy and comparable adverse events such as infection and cancer.
Dalia Eltahir
3 years ago
1. This is another study for the previous authors. Please summarise the conclusion of both studies.The authors in the these studies showed Belatacept based regimen is not inferior than CsA-based regimen in patient survival and graft survival. In their first study (2005)the rate of rejection at 6 months was similar between treatment groups and concluded that Belatacept was not inferior in prevention of AR, moreover stated that subconical rejection is more common with less intensive regimen of Belatacept. In their second study(2006-2008) the authors made a different conclusion, that the incidence of acute rejection was higher in the recipients of Belatacept.The prevalence of biopsy-proven chronic allograft nephropathy at month 12 was lower in the belatacept groups compared with CsA. Suggest a role of belatacept in the management of renal transplantation. Belatacept can give a immunosuppressive efficacy in renal-transplant recipients similar to that afforded by cyclosporine, but with more benefits in cardiovascular and metabolic risk profiles, preservation of kidney function, and low incidence of chronic allograft nephropathy.
Amit Sharma
3 years ago
1. This is another study for the previous authors. Please summarise the conclusion of both studies.
Costimulation Blockade with Belatacept in Renal Transplantation (2005)
This was non-inferiority trial, comparing short-term effects of belatacept based regimens as compared to cyclosporine based regimen on graft function and graft rejection as well as the cardiovascular and metabolic profile of the patient. The study concluded that belatacept was non-inferior to cyclosporine in preventing acute rejection, with better graft function at end of study period, less rates of chronic allograft nephropathy and better cardiovasular and metabolic profile.
A Phase III Study of Belatacept-based Immunosuppression Regimens versus Cyclosporine in Renal Transplant Recipients (BENEFIT Study) (2010)
In this trial, at 12 months post-transplant, as compared to the cyclosporine group, the belatacept group had better GFR, decreased chronic allograft nephropathy, similar patient and graft survival, increased PTLD, with increased rates and grades of acute rejection. The belatacept group patients had better blood pressure and lipid control while increased adverse events were seen in cyclosporine group. The authors concluded that, as compared to cyclosporine based regimen, Belatacept based immunosuppression regimen is safe and effective in kidney transplants with respect to patient and graft survival having a better graft function, cardiovascular and metabolic profile inspite of increased risk of acute rejections.
So, the difference with this longer-term follow-up was increased rates and grades of acute rejection and increased episodes of PTLD in belatacept group.
2. Suggest a role of belatacept in the management of renal transplantation.
In light of these two studies, the role of belatacept in kidney transplantation is with patients having low risk and EBV positive serology.
It can be used especially in low-risk patients with poor cardiovascular parameters (dyslipidemia and hypertension)
Last edited 3 years ago by Amit Sharma
Hinda Hassan
3 years ago
This is another study for the previous authors. Please summarise the conclusion of both studies.
This study showed that belatacept was not inferior to cyclosporine with respect to the incidence of acute rejection at six months while in BENEFIT, belatacept had more acute rejection at 12 months
The mGFR at one year was higher with belatacep which would result in improved graft survival of three to four years. This was also noticed in BENEFIT.
Belatacep has similar or reduced cholesterol levels and blood pressure to cyclosporine while in BENEFIT, it was associated with a better cardiovascular and metabolic profile than cyclosporine. Suggest a role of belatacept in the management of renal transplantation.
.
Belatacept is similar cyclosporine with lower cardiovascular and metabolic side effects. So it can be used in patient with high risk of CVS and metabolic complications provided that they have no contraindication for belatacept.
Assafi Mohammed
3 years ago
This is another study for the previous authors. Please summarise the conclusion of both studies.? The authors in the these studies showed superiority of Belatacept based regimen in comparison to CsA-based regimen in acheiving good renal function and maintaining better patient survival and graft survival. In their first study (2005)the rate of rejection at 6 months was similar between treatment groups and concluded that Belatacept was not inferior in prevention of AR, moreover stated that subconical rejection is more common with less intensive regimen of Belatacept. In their second study(2006-2008) the authors made a different conclusion, that the incidence of acute rejection was higher in the recipients of Belatacept.The prevalence of biopsy-proven chronic allograft nephropathy at month 12 was lower in the belatacept groups compared with CsA. ?comparison between BENIFIT AND BENEFIT-EXT) The role of belatacept in the management of renal transplantation:
The first marketed intravenous maintenance immunosuppressant.
Option for maintenance immunosuppression in adult KTR.It is approved for use in combination with basiliximab induction, mycophenolate mofetil, and corticosteroids to prevent rejection in adult KTR.
Maintaining renal function after transplant and reducing some of the metabolic side effects of CNIs related to hypertension and dyslipidemia (BENEFIT).
Weam Elnazer
3 years ago
At six months, acute rejection occurred in 7% of intensive belatacept patients, 6% of less intense belatacept patients, and 8% of cyclosporine patients. At 12 months, both intensive and less intense belatacept regimens had higher glomerular filtration rates than cyclosporine (66.3, 62.1, and 53.5 ml per minute per 1.73 m2, respectively), and chronic allograft nephropathy was less prevalent with belatacept than with cyclosporine (29 per cent, 20 per cent, and 44 per cent, respectively). Despite the cyclosporine group’s larger usage of lipid-lowering and antihypertensive drugs, belatacept groups had equal or lower cholesterol and blood pressure readings.
conclusions
Belatacept did not seem to be inferior to cyclosporine in avoiding acute rejection following renal transplantation. Belatacept may minimize chronic allograft nephropathy and maintain the glomerular filtration rate.
Role in renal transplantation:
-It prevents T cell activation by preventing the binding of CD28 on T cells and CD86,80 on APC.
. used in low-moderate immunological risk transplants(Exclude the donor EBV + V to EBV -VE).
Can be used in renal transplantation as a maintenance therapy especially if there is evidence of CNI toxicity.
if there is a contraindication for CNI, like PRES(developed due to CNI).
Doaa Elwasly
3 years ago
-The conclusion of this study is that belatacept is as efficient as cyclosporine in reducing the incidence of biopsy-proven acute rejection at six months with favourable effects on cardiovascular ,metabolic profile and renal function with lower incidence of chronic allograft nephropathy
The conclusion of BENEFIT study is that belatacept was associated with the same patient and graft survival, better renal function, a trend toward less chronic allograft nephropathy and an improved cardiovascular and metabolic profile compared with cyclosporine at 1 year posttransplant, in spite of increasing the acute rejection in the early posttransplant period.
-Belatacept binds avidly to CD80 and CD8than abatacept so it is a more potent inhibitor of T-cell activation, and effective rejection prophylaxis in non humans leading to preservation of renal function and decreasing the occurrence of chronic allograft nephropathy with less side effects in suitable doses.
Ahmed Omran
3 years ago
1-The 2 studies by same authors explored the effects of co stimulation blocking using belatacept regarding renal function ,graft rejection &survival ,side effects and metabolic profile at different intervals.
Conclusion:
Compared to conventional cyclosporine group:
Comparable findings were in incidence of acute rejection at 6 months ,graft survival at 6&12 months and metabolic profile in addition to cardiovascular risk factors.
High GFR at 6&12 months ,higher incidence of acute rejection at 12 months and increased incidence of CNSPTLD in belatacept group.
Lower prevalence of chronic allograft nephropathy in belatacept group.
2-Based on its concluded criteria, and in spite of its relative safety ,it could be suggested ;as a wise implementation, to limit its use in low risk recipients with positive EBV serology.
Use for maintenance immunosuppression is approved for use in combination with basiliximab induction, mycophenolate mofetil, and corticosteroids .
Reduction of some metabolic side effects of CNIs( hypertension and dyslipidemia).
Abdulrahman Ishag
3 years ago
This is another study for the previous authors. Please summarise the conclusion of both studies.
This study suggests 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. BENEFIT suggests that belatacept is associated with superior renal function and similar patient / graft survival versus cyclosporine at 1 year ,despite a higher rate of early acute rejection .
Suggest a role of belatacept in the management of renal transplantation.
belatacept can provide a level of immunosuppressive efficacy in renal-transplant recipients similar to that afforded by cyclosporine, but with the potential benefits of improved cardiovascular and metabolic risk profiles, greater preservation of kidney function, and a lower incidence of chronic allograft nephropathy.
Heba Wagdy
3 years ago
Please summarise the conclusion of both studies.
In this study
Belatacept and cyclosporine had similar effectiveness in preventing acute rejection, preserving renal allograft function and decreasing the rate of allograft nephropathy with avoidance of adverse cardiovascular and metabolic effects In BENEFIT study
Belatacept had better preservation of kidney function than cyclosporine, both had the same graft and patient survival with better cardiovascular and metabolic profile than cyclosporine but was associated with higher rate of early acute rejection.
Suggest a role of belatacept in the management of renal transplantation.
Belatacept may replace cyclosporine in maintenance therapy after transplant
Conversion of CNI to belatacept to avoid CNI toxicity on renal allograft
the high risk of acute rejection is a concern, also associated with increased risk of PTLD
Ban Mezher
3 years ago
Both studies evaluate the effect of belatacept on incidence of acute rejection when compared to cyclosporine , but one study assess the risk in first 6 months & the second assess it in 12 months post transplantation.
Conclusion of both studies:
both drugs have similar incidence of AR in first 6 months but the risk increased after 12 months post transplantation.
improved CV, metabolic profile & GFR in patients treated with belatacept
CAN rate less in patients treated with belatacept.
similar risk of infection in both drugs
similar patients & graft survival
increase risk of PTLD in patients treated with belatacept intensive regime.
Belatacept is second generation co-stimulatory blocker that inhibit T cell activation through binding of CD80/CD86 on APC result in signal 2 failure. At 2011 FDA approved using of belatacept as alternative to CNI based regime to prevent rejection & reduce renal & non renal complication caused by CNI.
Mohamad Habli
3 years ago
This study demonstrates the renal outcomes in the early post-transplant period, up to 6 months, where is the previous study reported the renal outcomes at longer followup- at one year.
Both studies done by the same team reported renal function at several intervals, incidence of rejection, graft survival, adverse events and metabolic profile.
Summary of both conclusions
-eGFR at 6 and 12 months was higher in belatacept groups when compared to the conventional cyclosporine group
-The incidence of acute rejection, was similar at 6 months in both groups however it was higher in belatacept groups at 1 year when compared to conventional cyclosporine group
-Graft survival rate was similar in both groups at 6 and 12 months.
-Belatacept based regimen was associated with increased incidence of CNS PTLD in both follow-up interval, comparing to the conventional cyclosporine group.
-Chronic allograft nephropathy prevalence was lower in the belatacept arm.
-Metabolic profile and cardiovascular risk factors were comparable between cyclosporine and belatacept groups.
Suggest a role of belatacept in the management of renal transplantation.
The role of Belatacept has been shown to be not superior or comparable to cyclosporin in terms of acute rejection at 1 year. In high risk patients ,where aggressive immunosuppression is needed, the use of Belatacept is associated with icrease risk of biopsy proven acute rejection, so it better to maintain the patient on CNI. The conversion to Belatacept from CNI was also studied in a randomized 3b trial showed that the risk of antibody mediated rejection is higher with Belatacept group. Although eGFR, graft survival and allograft nephropathy were reported to be better with Belatacept, the risk of rejection in high risk patients is of great impact on graft survival and renal outcomes.
Sherif Yusuf
3 years ago
This is another study for the previous authors. Please summarise the conclusion of both studies.
1. Graft survival was similar in both belatacept and conventional cyclosporine group
2. GFR was higher in belatacept groups when compared to the conventional cyclosporine group
3. Acute rejection rate was similar at 6 months post-transplantation but was higher in belatacept groups when compared to conventional cyclosporine group at 1 year
4. Both belatacept groups are associated with increased incidence of CNS PTLD when compared to the conventional cyclosporine based group
5. Incidence of CAN was lower in belatacept when compared to cyclosporine group
6. Cardiovascular risk factors including hypertension, hyperlipidemia were comparable between cyclosporine and belatacept groups Suggest a role of belatacept in the management of renal transplantation.
Belatacept should not be used in high-risk renal transplantation since the probability of occurrence of acute rejection with CNI avoidance is very high in this group, Moreover in high-risk transplantation we will use ATG with a subsequent increase in the incidence of PTLD
EBV negative recipients are more prone to the development of CNS PTLD, so it should be used in EBV positive recipients sonly
So… it can be given to low-risk EBV positive transplant recipient
Huda Al-Taee
3 years ago
This is another study for the previous authors. Please summarise the conclusion of both studies.
This study assessed the rate of acute rejection at 6 months and the GFR, chronic allograft nephropathy , and the metabolic status at 12 months among all the groups.
At 6 months: acute rejection rates were similar among the groups.
At 12 months: GFR was higher in belatacept group, chronic allograft nephropathy was lower in this group, lipid levels and BP were similar or slightly lower in belatacept group.
So belatacept shown to be non inferior to cyclosporine for prevention of acute rejection and it may preserve GFR and reduce the rate of chronic allograft nephropathy.
In BENEFIT Study:
The primary and secondary outcomes are assessed at 12 months.
Regarding the primary outcome:
patient and graft survival were similar between all the groups
renal function was better in belatacept group than cyclosporine group.
the rate of rejection was higher in belatacept group.
While the secondary outcome:
the mean measured GFR and the mean calculated GFR were higher in belatacept group.
the incidence of chronic allograft nephropathy was lower in belatacept group.
Suggest a role of belatacept in the management of renal transplantation
By preventing T cell activation, Belatacept can provide a level of immunosuppressionsimilar to that afford by cyclosporine but with potential benefit of improved cardiovascular and metabolic risk profiles, greater preservation of kidney function, and lower incidence of chronic allograft nephropathy.
Riham Marzouk
3 years ago
Mechanism of action : it is co stimulation block agent block co-stimulatory pathway by blocking binding between CD28 on T cell and CD86,80 on APC, so prevent T cell activation. Side effects : 1- anemia, urinary tract infection, hypertension, constipation, diarrhea, nausea and peripheral edema. 2- Acute infusion-related adverse events (within the first hour after belatacept infusion 3- malignancies (excluding nonmelanoma skin cancer): posttransplant lymphoproliferative 4- infections The precautions that should be taken before commencing such therapy: Not given in EBV negative patient to avoid development of PTLD Prophylactic treatment of CMV should be given Avoid or limit use of T cell depleting drugs
treatment with balatecept is safe, it has favorable effects on graft outcome with less toxicity than cyclosporine group, as it improves metabolic/cardiovascular profile.
This is another study for the previous authors. Please summarise the conclusion of both studies. Conclusion from this study –
Belatacept can provide a level of immunosuppressive efficacy in renal-transplant recipients similar to that afforded by cyclosporine. Patients treated with belatacept regimens had rates of acute rejection similar to those among patients taking cyclosporine.
Potential benefits of Belatacept include-
improved cardiovascular and metabolic risk profiles-cholesterol levels and blood pressure were
similar or slightly lower in the belatacept groups than in the cyclosporine group.
greater preservation of kidney function- The measured glomerular filtration rate at one year was
approximately 9 to 13 ml per minute higher among recipients of belatacept than among cyclosporine recipients.
lower incidence of chronic allograft nephropathy.
Conclusion from the previous study –
Belatacept was associated with
superior renal function
similar patient/graft survival versus cyclosporine at 1 year posttransplant
Higher rate of early acute rejection.
There was a higher incidence of PTLD in belatacept patients with known risk factors.
Overall safety was same as compared to cyclosporine Suggest a role of belatacept in the management of renal transplantation.
Has a role in CNI avoidance protocol in renal transplantation.
Belatacept should be administered in combination with Basiliximab induction, mycophenolate mofetil (MMF), and corticosteroids. Corticosteroid doses can be tapered to approximately 15 mg (10-20 mg) per day by the first 6 weeks and then at approximately 10 mg (5-10 mg) per day for the first 6 months posttransplant.
Costimulation Blockade with Belatacept in Renal Transplantation
This is another study for the previous authors. Please summarize the conclusion of both studies.
Suggest a role of belatacept in the management of renal transplantation.
Belatacept is selective costimulatory blockade agent that inhibit T cell activation at CD28- CD80 -CD86 pathway.
This study randomized partially blinded multicenter phase 11 trial to assess the efficacy of belatacept with CNI withdraw in preventing acute rejection at 6 months as primary objective and secondary objective was to assess its effect on graft and patient survival at 12 months, also assess the rate of Chronic allograft nephropathy and other metabolic risk like cardiovascular event, HTN and dyslipidemia
They divided the patients in to three groups 1.1.1 the more intense belatacept group, low intense belatacept group and cyclosporine group, all received induction with basiliximab ( IL2 inhibitors ) followed by MPA and steroid ,this study conclude that the belatacept in both intense and low dose was noninferiority than cyclosporine in prevention of acute rejection at first 6 months and better measured GFR in both belatacept group than cyclosporine but similar impact on graft and patient survival at 12 months with lower incidence of CAN in both belatacept arms and less metabolic complication like dyslipidemia and HTN compared to cyclosporine group
Belatacept its promising immunosuppressive agent that can be used with CNI avoidance or CNI minimization or sparing protocol but preferred to be compared with the more potent CNI agent like tacrolimus as its now consider standard maintenance therapy with proven efficacy in lowering the acute rejection rate compared to cyclosporine .
Belatacept represents a new class of primary
immunosuppressants, arguably the first since the
introduction of cyclosporine, the first calcineurin
inhibitor. Whereas calcineurin inhibitors block or
diminish the effects of T-cell activation on allografts, belatacept prevents T-cell activation.
accomplished without concurrent global immunosuppression of T-cell–depletion strategies. Our results suggest that belatacept can provide a level of
immunosuppressive efficacy in renal-transplant
recipients similar to that afforded by cyclosporine,
but with the potential benefits of improved cardiovascular and metabolic risk profiles, greater preservation of kidney function, and a lower incidence of chronic allograft nephropathy
Suggest a role of belatacept in the management of renal transplantation.
Kidney transplant, prophylaxis of organ rejection: IV: Note: Use in combination with basiliximab induction, mycophenolate mofetil, and corticosteroids.
Initial phase: 10 mg/kg on day 1 (day of transplant, prior to implantation) and on day 5 (~96 hours after day 1 dose), followed by 10 mg/kg at the end of week 2, week 4, week 8, and week 12 following transplantation
Maintenance phase: 5 mg/kg every 4 weeks (plus or minus 3 days) beginning at the end of week 16 following transplantation
.
References
Combs J, Kagan A, Boelkins M, Coscia L, Moritz M, Hofmann RM. Belatacept during pregnancy in renal transplant recipients: two case reports. Am J Transplant. 2018;18(8):2079-2082. doi:10.1111/ajt.14911 [PubMed 29719109]
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(3):547-57. [PubMed 20415898]
Enderby CY, Habib P, Patel PC, Yip DS, Orum S, Hosenpud JD. Belatacept maintenance in a heart transplant recipient. Transplantation. 2014;98(7):e74-75. [PubMed 25285956]
1- This is another study for the previous authors. Please summarise the conclusion of both studies.
1- the incidence of acute rejection, in the 1st 6 months, was similar to Cyclopsorine.
2- eGFR was even higher at 1 year post-transplantation with Belatacept.
3- the incidence of chronic allograft nephropathy was lower with using Belatacept as compared to CNIs.
4- the incidence of dyslipidemia and hypertension was almost similar to that of cyclosporine.
2- Suggest a role of belatacept in the management of renal transplantation.
Q1: This study showed that belatacept is non- inferior to cyclosporine in terms of acute rejection at six months. Belatacept was better than cyclosporine in regard to one year GFR and chronic allograft nephropathy. Eventually belatacept was slightly better than cyclosporine in lipid or blood pressure levels. Previous study showed no difference between patients and graft survival or one year renal function between groups. Lower cardiovascular or metabolic adverse effects but more acute rejection rates during first year were seen in belatacept group. Both showed safety of belatacept as a new immunosuppressant drug.
Q2: Belatacept is considered as a CNI –sparing immunosuppressant protocol to reduce nephrotoxicity of CNIs .Also, non – adherent patients could be considered for this treatment because of 4-6weeks injection intervals for belatacept. This could be in form of CNI avoidance, CNI -minimization or CNI – conversion protocols.
This study involved 218 patients divided into 3 treatment groups receiving belatacept intense dose , low dose and cyclosporin.
They estimated the incidence of acute rejection 6 month post transplant in the 3 groups and they found it s similar in the 3 groups making belatacept non inferior to cyclosporin as regards incidence of acute rejection, more over the beleatacept groups maintained higher GFR than cyclosporin group .
They concluded that belatacept could perform the same as cyclosporin regarding preventing acute rejections, with the benefit that less cardiovascular side effects .
The previous study concluded that belatacept treated patients was same as cyclosporin regarding patient and graft survival ,
Better regarding occurrence of renal impairment,
And inferior to cyclosporin regarding incidence of acute rejection.
Role of belatacept in transplant patients is to provide same degree of immunosuppression as cyclosporine without the CNI associated side effects.
Conclusion:-Belatacept, a selective costimulation blocker, binds surface costimulatory ligands (CD80 and CD86) of antigen-presenting cells. Belatacept and cyclosporine had a similar rate of acute rejection, infections, and malignancy.
Belatacept may allow patients to avoid the adverse renal, cardiovascular, and metabolic effects of cyclosporine. The measured glomerular filtration rate at one year was higher among recipients of belatacept than among cyclosporine recipients. Belatacept reduces cholesterol and Blood pressure than cyclosporine.
a role of belatacept in the management of renal transplantation :
Belatacept can provide a level of immunosuppressive efficacy in renal-transplant recipients similar to that afforded by cyclosporine, but with the potential benefits of improved cardiovascular and metabolic risk profiles, greater preservation of kidney function, and a lower incidence of chronic allograft nephropathy.
This is another study for the previous authors. Please summarise the conclusion of both studies.
Costimulation Blockade with Belatacept in Renal Transplantation (2005)
This was non-inferiority trial which compared short-term effects of belatacept based regimens as compared to cyclosporine-based regimen on graft function and acute rejection whilst evaluating the cardiovascular and metabolic effects of the both drugs . Belatacept was shown non-inferior to cyclosporine in preventing acute rejection, with better graft function with less rates of chronic allograft nephropathy and less effects cardiovascular and metabolic profile.
A Phase III Study of Belatacept-based Immunosuppression Regimens versus Cyclosporine in Renal Transplant Recipients (BENEFIT Study) (2010)
GTiral evaluated participants 12 months post-transplant which showed belatacept treated patients had better GFR, less chronic allograft nephropathy but similar patient, and graft survival compred to CyA treated group. The belatacept group ad better blood pressure and lipid control. The study concluded that belatacept based immunosuppression regimen is safe and effective in kidney transplants : patient and graft survival, cardiovascular and metabolic profile despite of increased risk of acute rejections.
2. Suggest a role of belatacept in the management of renal transplantation.
Belatacept has role in CNI avoidance therapy for those who has adverse effect or metabolic complications of CNIs.
Costimulation Blockade with Belatacept in Renal Transplantation
The primary objective of this study was to demonstrate the noninferiority of belatacept over cyclosporine with respect to the incidence of acute rejection at six months results suggest that the two agents are similarly effective for the prevention of acute rejection.
Patients treated with belatacept regimens had rates of acute rejection similar to those among patients taking cyclosporine.
subclinical rejection occured with less intensive regimen didn’t affect graft survival or increased the risk of chronic allograft nephropathy.
In this study it was suggested that use of belatacept was superior to cyclosporine as regards the adverse renal, cardiovascular, and metabolic effects of cyclosporine.
The measured GFR at one year was approximately 9 to 13 ml per minute higher among recipients of belatacept than among cyclosporine recipients.
Since the GFR generally declines by approximately 3 ml per minute per 1.73 m2 per year in transplant recipients, these differences, if sustained, could result in improved allograft survival of three to four years.
They also found similar rate of infections and cancer among the groups and PTLD occurred mainly patients with predisposing risk factors to PTLDS (primary Epstein–Barr virus infection or treatment with muromonab-CD3)
In the previous study the authors concluded, that the incidence of acute rejection was higher in the recipients of Belatacept.
The prevalence of biopsy-proven chronic allograft nephropathy at month 12 was lower in the belatacept groups
And PTLD was higher in belatacept group .
And the both studies showed the same results on better effect of balatacept over cyclosporine in metabolic , cardiovascular risk and lipid profile
Suggest a role of belatacept in the management of renal transplantation.
Belatacept can provide a level of immunosuppressive efficacy in renal-transplant recipients similar cyclosporine, with less cardiovascular and metabolic risk profiles and greater preservation of kidney function, a lower incidence of chronic allograft nephropathy and comparable adverse events such as infection and cancer.
This is another study for the previous authors. Please summarise the conclusion of both studies.
A total of 218 patients were enrolled in this study undergoing kidney transplantation of standard risk . randomly divided into 3 groups, to compare the effect of intensive and low intensive Balatacept Vs cyclosporins mentainence regimens. For one year follow duration
At six months, the incidence of acute rejection was similar among the . At 12 months, the glomerular filtration rate was significantly higher with both intensive and less-intensive belatacept than it was with cyclosporine chronic allograft nephropathy was less common with both regimens of belatacept than with cyclosporine
Both studies concluded that Balatacept , a selective T cell inactivator (selective costimulation blocker) when used in menaintenance immune suppression among standerd risk recipients didn’t show inferiority to cyclosporine as egard prevention of graft rejection within the first 6 momnths post trnsplantation
On the other hand shows superiority over cyclosporins as regard preservation of graft function with less declining rates in GFR in one year post Tx, less incidence of chronic transplant glomerulopathy.
Most importantly Belatacept showed improved cardiovascular/metabolic risk profile than Cyclosporins , belatacept was generally safe, although there was a higher incidence of PTLD but were mostly among patients with predisposing risk factors to PTLDS (primary Epstein–Barr virus infection or treatment with muromonab-CD3) (1), and was related to the levels of immunosuppression.(2)
Balatacept was safe to use , no clinical significant difference in incidence of infection compared to cyclosporine, no recorded sever reactions related to infusion. However patients show better metabolic profile , lipid levels, BP levels incidence of NOPTD than cyclosporin
Suggest a role of belatacept in the management of renal transplantation.
Standerd risk transplant reciepientspreferred to be mentained on Cyclosporin sparing immunesuppression mentainenca regimens prone to cardiovascular , cerebrovascular dyslipdemia, or other metabolic derangements. To prevent CNIs adverse effects.
References:
(1). Walker RC, Paya CV, Marshall WF, et al. Pretransplantation seronegative Epstein-Barr virus status is the primary risk factor for posttransplantation lymphoproliferative disorder in adult heart, lung, and other solid organ transplantations. J Heart Lung Transplant 1995;14:214-21.
(2). Herzig KA, Juffs HG, Norris D, et al. A single-centre experience of post-renal transplant lymphoproliferative disorder. Transpl Int 2003;16:529-36.
Costimulation Blockade with Belatacept in Renal Transplantation
Summarize the conclusion
Belatacept is not inferior to cyclosporine in view of preventing acute rejection after
kidney
transplantation. it maintains the glomerular filtration rate and decreases the
rate of chronic allograft nephropathy.
The study suggests that the belatacept and
cyclosporine has a similar effect in the prevention of acute rejection.
With the use of belatacept, the patients may
avoid the adverse effect of cyclosporine (renal, cardiovascular, and metabolic).
The GFR at one year was about 9 to 13 ml per
minute higher among recipients on belatacept than those on cyclosporine. As
belatacept is a non-nephrotoxic drug
Serum cholesterol levels and blood pressure
were similar or slightly lower in the belatacept recipients than in
cyclosporine recipients in spite of their use of the lipid-lowering drugs as
well, the antihypertensive drugs.
Belatacept has the same incidence of cancer
as the cyclosporine length and intensity of the immunosuppressive drugs
contribute to this risk, and a similar rate of infection as well.
In recipients receiving less-intensive
therapy, subclinical rejection did not appear to have an adverse effect on
graft survival or the risk of chronic allograft nephropathy.
The author comment that the difference
between belatacept and cyclosporine therapy should be regarded as suggestive
rather than definitive.
Suggest a role of belatacept in the management of renal
transplantation.
The study suggests that belatacept can lead
to a level of immunosuppressive efficacy similar to that achieved by the
cyclosporine, and with potential benefits on cardiovascular and metabolic
profiles, greater maintenance of renal function, and a lower incidence of
chronic allograft nephropathy.
1. This is another study for the previous authors. Please summaries the
conclusion of both studies.
Maintenance immunosuppression with CNI yields excellent one-year survival, it is
associated over the long term with high rates of death and graft loss, owing in part to the
adverse renal, cardiovascular, and metabolic effects of these agents.
Use of Belatacept cell blocker which less toxic, may preserve the glomerular filtration
rate and reduce the rate of chronic allograft nephropathy.
In BENEFIT, one of the largest studies in kidney allograft recipients, belatacept was
associated with similar patient and graft survival, superior renal function, a trend toward
less chronic allograft nephropathy and an improved cardiovascular and metabolic profile
compared with cyclosporine 1 year post transplant.
2-Suggest a role of belatacept in the management of renal transplantation.
Belatacept can provide a level of immunosuppressive efficacy in renal-transplant
recipients similar to that afforded by cyclosporine, but with the potential benefits of
improved cardiovascular and metabolic risk profiles, greater preservation of kidney
function, and a lower incidence of chronic allograft nephropathy.
Can be applied in clinical practice if more RCT shows same benefit, especially if
compared to TAC, which more used now and more effective and less toxicity compare to
Cyclosporine.
Co-stimulation Blockade with Belatacept in Renal Tx
This was a non-inferiority trial, comparing short-term effects of belatacept based regimens as compared to cyclosporine based regimen on graft function and graft rejection as well as the cardiovascular and metabolic profile of the patient. The study concluded that belatacept was non-inferior to cyclosporine in preventing acute rejection, with better graft function at end of study period, less rates of CAN.
BENEFIT Study
A randomized controlled, parallel group, multicenter, Phase III study conducted over 3 years.
Aim: To assess effect of Belatacept on graft renal function and its long-term effects vs CNI on. patient and graft survival, acute rejection rates, malignancies and infections.
Out of 738 recruited patients, 686 were randomized in 3 groups, namely more intensive (MI), and low intensive (LI) Belatacept regimen and cyclosporine group. Additionally, all were given induction with basiliximab and were on MMF and steroids.
At 12 months post-transplant, the study showed that as compared to the cyclosporine group, the belatacept group had better GFR, decreased chronic allograft nephropathy similar patient and graft survival, increased PTLD, with increased rates and grades of acute rejection.
Conclusion: As compared to cyclosporine based regimen, Belatacept based immunosuppression regimen is safe and effective in kidney transplants with respect to patient and graft survival having a better graft function, cardiovascular and metabolic profile inspite of increased risk of acute rejections.
Suggest a role of belatacept in the management of renal transplantation:
the role of belatacept in kidney transplantation is with patients having low risk.
It can be used especially in low-risk patients with IHD , Dyslipidemia or metabolic syndrome .
In the previous study, both Belatacept regimens were associated with better patient and graft survival, superior kidney function, higher incidence of acute rejection episodes, a trend toward less chronic allograft nephropathy and an improved cardiovascular and metabolic profile compared with cyclosporine-based treatment.
This study reported similar results, such as better preservation of GFR, reduced chronic allograft nephropathy in Belatacept groups compared to cyclosporine. The metabolic profile was similar between two groups. In addition, the risk of acute rejection was similar among groups in contrast to previous study (higher incidence of acute rejection in Belatacept groups).
This study showed noninferiority of Belatecept over cyclosporine with respect to the incidence of acute rejection. The frequency of infections and cancers were similar between groups. Cancers including PTLD occur in belatacept groups in a dose dependent fashion and PTLD was associated with EBV infection.
The use of belatacept may allow patients to avoid adverse renal, cardiovascular, and metabolic effects of cyclosporine.
In contrast to cyclosporin which diminishes the effect of T cell activation on graft, belatacept prevents T cell activation. Belatacept can provide a level of immunosuppressive efficacy in renal-transplant recipients similar to that afforded by cyclosporine, but with the potential benefits of improved cardiovascular and metabolic risk profiles, greater preservation of kidney function, a lower incidence of chronic allograft nephropathy and comparable adverse events such as infection and cancer.
1. This is another study for the previous authors. Please summarise the conclusion of both studies. The authors in the these studies showed Belatacept based regimen is not inferior than CsA-based regimen in patient survival and graft survival. In their first study (2005) the rate of rejection at 6 months was similar between treatment groups and concluded that Belatacept was not inferior in prevention of AR, moreover stated that subconical rejection is more common with less intensive regimen of Belatacept.
In their second study(2006-2008) the authors made a different conclusion, that the incidence of acute rejection was higher in the recipients of Belatacept.The prevalence of biopsy-proven chronic allograft nephropathy at month 12 was lower in the belatacept groups compared with CsA.
Suggest a role of belatacept in the management of renal transplantation. Belatacept can give a immunosuppressive efficacy in renal-transplant recipients similar to that afforded by cyclosporine, but with more benefits in cardiovascular and metabolic risk profiles, preservation of kidney function, and low incidence of chronic allograft nephropathy.
1. This is another study for the previous authors. Please summarise the conclusion of both studies.
Costimulation Blockade with Belatacept in Renal Transplantation (2005)
This was non-inferiority trial, comparing short-term effects of belatacept based regimens as compared to cyclosporine based regimen on graft function and graft rejection as well as the cardiovascular and metabolic profile of the patient. The study concluded that belatacept was non-inferior to cyclosporine in preventing acute rejection, with better graft function at end of study period, less rates of chronic allograft nephropathy and better cardiovasular and metabolic profile.
A Phase III Study of Belatacept-based Immunosuppression Regimens versus Cyclosporine in Renal Transplant Recipients (BENEFIT Study) (2010)
In this trial, at 12 months post-transplant, as compared to the cyclosporine group, the belatacept group had better GFR, decreased chronic allograft nephropathy, similar patient and graft survival, increased PTLD, with increased rates and grades of acute rejection. The belatacept group patients had better blood pressure and lipid control while increased adverse events were seen in cyclosporine group. The authors concluded that, as compared to cyclosporine based regimen, Belatacept based immunosuppression regimen is safe and effective in kidney transplants with respect to patient and graft survival having a better graft function, cardiovascular and metabolic profile inspite of increased risk of acute rejections.
So, the difference with this longer-term follow-up was increased rates and grades of acute rejection and increased episodes of PTLD in belatacept group.
2. Suggest a role of belatacept in the management of renal transplantation.
In light of these two studies, the role of belatacept in kidney transplantation is with patients having low risk and EBV positive serology.
It can be used especially in low-risk patients with poor cardiovascular parameters (dyslipidemia and hypertension)
This is another study for the previous authors. Please summarise the conclusion of both studies.
This study showed that belatacept was not inferior to cyclosporine with respect to the incidence of acute rejection at six months while in BENEFIT, belatacept had more acute rejection at 12 months
The mGFR at one year was higher with belatacep which would result in improved graft survival of three to four years. This was also noticed in BENEFIT.
Belatacep has similar or reduced cholesterol levels and blood pressure to cyclosporine while in BENEFIT, it was associated with a better cardiovascular and metabolic profile than cyclosporine.
Suggest a role of belatacept in the management of renal transplantation.
.
Belatacept is similar cyclosporine with lower cardiovascular and metabolic side effects. So it can be used in patient with high risk of CVS and metabolic complications provided that they have no contraindication for belatacept.
This is another study for the previous authors. Please summarise the conclusion of both studies.?
The authors in the these studies showed superiority of Belatacept based regimen in comparison to CsA-based regimen in acheiving good renal function and maintaining better patient survival and graft survival. In their first study (2005) the rate of rejection at 6 months was similar between treatment groups and concluded that Belatacept was not inferior in prevention of AR, moreover stated that subconical rejection is more common with less intensive regimen of Belatacept.
In their second study(2006-2008) the authors made a different conclusion, that the incidence of acute rejection was higher in the recipients of Belatacept.The prevalence of biopsy-proven chronic allograft nephropathy at month 12 was lower in the belatacept groups compared with CsA.
?comparison between BENIFIT AND BENEFIT-EXT)
The role of belatacept in the management of renal transplantation:
At six months, acute rejection occurred in 7% of intensive belatacept patients, 6% of less intense belatacept patients, and 8% of cyclosporine patients. At 12 months, both intensive and less intense belatacept regimens had higher glomerular filtration rates than cyclosporine (66.3, 62.1, and 53.5 ml per minute per 1.73 m2, respectively), and chronic allograft nephropathy was less prevalent with belatacept than with cyclosporine (29 per cent, 20 per cent, and 44 per cent, respectively). Despite the cyclosporine group’s larger usage of lipid-lowering and antihypertensive drugs, belatacept groups had equal or lower cholesterol and blood pressure readings.
conclusions
Belatacept did not seem to be inferior to cyclosporine in avoiding acute rejection following renal transplantation. Belatacept may minimize chronic allograft nephropathy and maintain the glomerular filtration rate.
-It prevents T cell activation by preventing the binding of CD28 on T cells and CD86,80 on APC.
. used in low-moderate immunological risk transplants(Exclude the donor EBV + V to EBV -VE).
-The conclusion of this study is that belatacept is as efficient as cyclosporine in reducing the incidence of biopsy-proven acute rejection at six months with favourable effects on cardiovascular ,metabolic profile and renal function with lower incidence of chronic allograft nephropathy
The conclusion of BENEFIT study is that belatacept was associated with the same patient and graft survival, better renal function, a trend toward less chronic allograft nephropathy and an improved cardiovascular and metabolic profile compared with cyclosporine at 1 year posttransplant, in spite of increasing the acute rejection in the early posttransplant period.
-Belatacept binds avidly to CD80 and CD8than abatacept so it is a more potent inhibitor of T-cell activation, and effective rejection prophylaxis in non humans leading to preservation of renal function and decreasing the occurrence of chronic allograft nephropathy with less side effects in suitable doses.
1-The 2 studies by same authors explored the effects of co stimulation blocking using belatacept regarding renal function ,graft rejection &survival ,side effects and metabolic profile at different intervals.
Conclusion:
Compared to conventional cyclosporine group:
2-Based on its concluded criteria, and in spite of its relative safety ,it could be suggested ;as a wise implementation, to limit its use in low risk recipients with positive EBV serology.
This is another study for the previous authors. Please summarise the conclusion of both studies.
This study suggests 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.
BENEFIT suggests that belatacept is associated with superior renal function and similar patient / graft survival versus cyclosporine at 1 year ,despite a higher rate of early acute rejection .
Suggest a role of belatacept in the management of renal transplantation.
belatacept can provide a level of immunosuppressive efficacy in renal-transplant recipients similar to that afforded by cyclosporine, but with the potential benefits of improved cardiovascular and metabolic risk profiles, greater preservation of kidney function, and a lower incidence of chronic allograft nephropathy.
In this study
Belatacept and cyclosporine had similar effectiveness in preventing acute rejection, preserving renal allograft function and decreasing the rate of allograft nephropathy with avoidance of adverse cardiovascular and metabolic effects
In BENEFIT study
Belatacept had better preservation of kidney function than cyclosporine, both had the same graft and patient survival with better cardiovascular and metabolic profile than cyclosporine but was associated with higher rate of early acute rejection.
Belatacept may replace cyclosporine in maintenance therapy after transplant
Conversion of CNI to belatacept to avoid CNI toxicity on renal allograft
the high risk of acute rejection is a concern, also associated with increased risk of PTLD
Both studies evaluate the effect of belatacept on incidence of acute rejection when compared to cyclosporine , but one study assess the risk in first 6 months & the second assess it in 12 months post transplantation.
Conclusion of both studies:
Belatacept is second generation co-stimulatory blocker that inhibit T cell activation through binding of CD80/CD86 on APC result in signal 2 failure. At 2011 FDA approved using of belatacept as alternative to CNI based regime to prevent rejection & reduce renal & non renal complication caused by CNI.
This study demonstrates the renal outcomes in the early post-transplant period, up to 6 months, where is the previous study reported the renal outcomes at longer followup- at one year.
Both studies done by the same team reported renal function at several intervals, incidence of rejection, graft survival, adverse events and metabolic profile.
Summary of both conclusions
-eGFR at 6 and 12 months was higher in belatacept groups when compared to the conventional cyclosporine group
-The incidence of acute rejection, was similar at 6 months in both groups however it was higher in belatacept groups at 1 year when compared to conventional cyclosporine group
-Graft survival rate was similar in both groups at 6 and 12 months.
-Belatacept based regimen was associated with increased incidence of CNS PTLD in both follow-up interval, comparing to the conventional cyclosporine group.
-Chronic allograft nephropathy prevalence was lower in the belatacept arm.
-Metabolic profile and cardiovascular risk factors were comparable between cyclosporine and belatacept groups.
Suggest a role of belatacept in the management of renal transplantation.
The role of Belatacept has been shown to be not superior or comparable to cyclosporin in terms of acute rejection at 1 year. In high risk patients ,where aggressive immunosuppression is needed, the use of Belatacept is associated with icrease risk of biopsy proven acute rejection, so it better to maintain the patient on CNI. The conversion to Belatacept from CNI was also studied in a randomized 3b trial showed that the risk of antibody mediated rejection is higher with Belatacept group. Although eGFR, graft survival and allograft nephropathy were reported to be better with Belatacept, the risk of rejection in high risk patients is of great impact on graft survival and renal outcomes.
This is another study for the previous authors. Please summarise the conclusion of both studies.
1. Graft survival was similar in both belatacept and conventional cyclosporine group
2. GFR was higher in belatacept groups when compared to the conventional cyclosporine group
3. Acute rejection rate was similar at 6 months post-transplantation but was higher in belatacept groups when compared to conventional cyclosporine group at 1 year
4. Both belatacept groups are associated with increased incidence of CNS PTLD when compared to the conventional cyclosporine based group
5. Incidence of CAN was lower in belatacept when compared to cyclosporine group
6. Cardiovascular risk factors including hypertension, hyperlipidemia were comparable between cyclosporine and belatacept groups
Suggest a role of belatacept in the management of renal transplantation.
So… it can be given to low-risk EBV positive transplant recipient
This is another study for the previous authors. Please summarise the conclusion of both studies.
This study assessed the rate of acute rejection at 6 months and the GFR, chronic allograft nephropathy , and the metabolic status at 12 months among all the groups.
At 6 months: acute rejection rates were similar among the groups.
At 12 months: GFR was higher in belatacept group, chronic allograft nephropathy was lower in this group, lipid levels and BP were similar or slightly lower in belatacept group.
So belatacept shown to be non inferior to cyclosporine for prevention of acute rejection and it may preserve GFR and reduce the rate of chronic allograft nephropathy.
In BENEFIT Study:
The primary and secondary outcomes are assessed at 12 months.
Regarding the primary outcome:
While the secondary outcome:
the mean measured GFR and the mean calculated GFR were higher in belatacept group.
the incidence of chronic allograft nephropathy was lower in belatacept group.
Suggest a role of belatacept in the management of renal transplantation
By preventing T cell activation, Belatacept can provide a level of immunosuppression similar to that afford by cyclosporine but with potential benefit of improved cardiovascular and metabolic risk profiles, greater preservation of kidney function, and lower incidence of chronic allograft nephropathy.
Mechanism of action : it is co stimulation block agent block co-stimulatory pathway by blocking binding between CD28 on T cell and CD86,80 on APC, so prevent T cell activation.
Side effects :
1- anemia, urinary tract infection, hypertension, constipation, diarrhea, nausea and peripheral edema.
2- Acute infusion-related adverse events (within the first hour after belatacept infusion
3- malignancies (excluding nonmelanoma skin cancer): posttransplant lymphoproliferative
4- infections
The precautions that should be taken before commencing such therapy:
Not given in EBV negative patient to avoid development of PTLD
Prophylactic treatment of CMV should be given
Avoid or limit use of T cell depleting drugs
treatment with balatecept is safe, it has favorable effects on graft outcome with less toxicity than cyclosporine group, as it improves metabolic/cardiovascular profile.
This is another study for the previous authors. Please summarise the conclusion of both studies.
Conclusion from this study –
Belatacept can provide a level of immunosuppressive efficacy in renal-transplant recipients similar to that afforded by cyclosporine. Patients treated with belatacept regimens had rates of acute rejection similar to those among patients taking cyclosporine.
Potential benefits of Belatacept include-
improved cardiovascular and metabolic risk profiles-cholesterol levels and blood pressure were
similar or slightly lower in the belatacept groups than in the cyclosporine group.
greater preservation of kidney function- The measured glomerular filtration rate at one year was
approximately 9 to 13 ml per minute higher among recipients of belatacept than among cyclosporine recipients.
lower incidence of chronic allograft nephropathy.
Conclusion from the previous study –
Belatacept was associated with
superior renal function
similar patient/graft survival versus cyclosporine at 1 year posttransplant
Higher rate of early acute rejection.
There was a higher incidence of PTLD in belatacept patients with known risk factors.
Overall safety was same as compared to cyclosporine
Suggest a role of belatacept in the management of renal transplantation.
Has a role in CNI avoidance protocol in renal transplantation.
Belatacept should be administered in combination with Basiliximab induction, mycophenolate mofetil (MMF), and corticosteroids. Corticosteroid doses can be tapered to approximately 15 mg (10-20 mg) per day by the first 6 weeks and then at approximately 10 mg (5-10 mg) per day for the first 6 months posttransplant.