Belatacept

BACKGROUND: Efficacy and safety of belatacept have not been specifically reported for kidney transplantations from donors after circulatory death. METHODS: In this retrospective multicenter paired kidney study, we compared the outcome of kidney transplantations with a belatacept-based to a calcineurin inhibitor (CNI)-based immunosuppression. We included all kidney transplant recipients from donors after uncontrolled or controlled circulatory death performed in our center between February 2015 and October 2020 and treated with belatacept (n = 31)...

BACKGROUND: Belatacept (BTC), a fusion protein, selectively inhibits T-cell co-stimulation by binding to the CD80 and CD86 receptors on antigen-presenting cells (APCs) and has been used as immunosuppression in adult renal transplant recipients. However, data regarding its use in heart transplant (HT) recipients are limited. This retrospective cohort study aimed to delineate BTC's application in HT, focusing on efficacy, safety, and associated complications at a high-volume HT center. METHODS: A retrospective cohort study was conducted of patients who underwent HT between January 2017 and December 2021 and subsequently received BTC as part of their immunosuppressive regimen...

INTRODUCTION: . Despite the improvements of insulin therapy, people with type 1 diabetes (T1D) still suffer from a decreased quality of life and life expectancy. The search toward a cure for T1D is therefore still a scorching open field of research. AREAS COVERED: Tackling the immune checkpoint signaling pathways has gained importance in the field of cancer immunotherapy. The same pathways can be targeted in autoimmunity with an opposite principle: to dampen the exaggerated immune response...

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Though belatacept is administered with a weight-based dosing schema, there has been higher clearance reported in obese patients. Therefore, we evaluated the association between body mass index (BMI) and transplant outcomes in kidney transplant recipients who were randomized to cyclosporine- or belatacept-based immunosuppression in the BENEFIT and BENEFIT-EXT randomized clinical trials. A total of 666 and 543 patients underwent randomization and transplantation in BENEFIT and BENEFIT-EXT, respectively, of which 1056 had complete data and were included in this analysis...

BACKGROUND: Desensitization is one of the strategies to reduce antibodies and facilitate heart transplantation in highly sensitized patients. We describe our center's desensitization experience with combination of plasma cell (PC) depletion therapy (with proteasome inhibitor or daratumumab) and costimulation blockade (with belatacept). METHODS: We reviewed five highly sensitized patients who underwent desensitization therapy with plasma cell depletion and costimulation blockade...

BACKGROUND: Mixed lymphohematopoietic chimerism is a proven strategy for achieving operational transplant tolerance, though the underlying immunologic mechanisms are incompletely understood. METHODS: A post-transplant, non-myeloablative, tomotherapy-based total lymphoid (TLI) irradiation protocol combined with anti-thymocyte globulin and T cell co-stimulatory blockade (belatacept) induction was applied to a 3-5 MHC antigen mismatched rhesus macaque kidney and hematopoietic cell transplant model...

BACKGROUND: Conversion to a belatacept-based immunosuppression is currently used as a calcineurin inhibitors (CNI) avoidance strategy when the CNI-based standard of care immunosuppression is not tolerated after kidney transplantation. However, there is a lack of evidence on the long-term benefit and safety following conversion to belatacept. METHODS: We prospectively enrolled 311 kidney transplant recipients from 2007 to 2020 from two referral centers, converted from CNI to belatacept after transplant according to a prespecified protocol...

Heart transplantation (HTx) remains the last therapeutic resort for patients with advanced heart failure. The present work is a clinically focused review discussing current issues in heart transplantation. Several factors have been associated with the outcome of HTx, such as ABO and HLA compatibility, graft size, ischemic time, age, infections, and the cause of death, as well as imaging and laboratory tests. In 2018, UNOS changed the organ allocation policy for HTx. The aim of this change was to prioritize patients with a more severe clinical condition resulting in a reduction in mortality of people on the waiting list...

Belatacept, a modified form of CTLA-Ig that blocks CD28-mediated co-stimulation of T cells, is an immune-suppressant that can be used as an alternative to calcineurin inhibitors (CNIs). In kidney transplant recipients, belatacept has been associated with improved renal function and reduced cardiovascular toxicity. Monocytes as well as T-lymphocytes play causal roles in the pathophysiology of atherosclerotic disease. We hypothesized that the beneficial impact of the use of belatacept over CNIs on cardiovascular risk could be partly explained by the impact of belatacept therapy on these circulating leukocytes...

Tacrolimus, widely known as Prograf, has become the preferred immunosuppressant for preventing graft rejection in solid organ transplant recipients, particularly in steroid-sparing regimens. Its efficacy and reduced risk of acute and chronic rejection compared to cyclosporine have made it the preferred treatment option for transplant patients. However, tacrolimus has drawbacks as it is associated with adverse effects, such as renal tubular necrosis, kidney failure, hypertension, metabolic acidosis, and new-onset diabetes mellitus...

Belatacept is the first costimulatory blockade agent clinically approved for transplant immunosuppression. Although more than 10 years of study have demonstrated that belatacept offers superior long-term renal allograft and patient survival compared to conventional calcineurin inhibitor (CNI)-based immunosuppression regimens, the clinical adoption of belatacept has continued to lag because of concerns of an early risk of acute cellular rejection (ACR) and various logistical barriers to its administration. In this review, the history of the clinical development of belatacept is examined, along with the findings of the seminal BENEFIT and BENEFIT-EXT trials culminating in the clinical approval of belatacept...

Belatacept, a CTLA4-Ig, was designed to prevent rejection and graft loss in kidney transplant recipients. This immunotherapy showed a long-term clinical benefit mainly on renal function and better glycemic control but was also associated with a higher number of severe infectious diseases, particularly CMV disease, and lymphoproliferative disease. Therapeutic drug monitoring usually guides the benefit-risk assessment of long-term immunosuppression. In this study, an analytical method by LC-MS/MS was developed in 20 microL of plasma for the belatacept quantification...

OBJECTIVES: A common complication after transplant is an opportunistic infection, in part due to the necessary immunosuppression regimens that patients are placed on. This study aimed to assess the outcomes and rates of infection in kidney transplant recipients on belatacept compared with kidney transplant recipients on standard immunosuppression therapy. MATERIALS AND METHODS: We conducted a matched-pair case-control retrospective analysis of a prospectively recollected database of all adult kidney transplant patients at the SUNY Upstate Medical Hospital from January 1, 2016, to July 31, 2022...

BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation. The development of donor-specific antibodies (DSA) is a recognized risk factor for CLAD. Based on experience in kidney transplantation, we hypothesized that belatacept, a selective T-cell costimulatory blocker, would reduce the incidence of DSA after lung transplantation, which may ameliorate the risk of CLAD. METHODS: We conducted a pilot randomized controlled trial (RCT) at 2 sites to assess the feasibility and inform the design of a large-scale RCT...

To address the challenges of assessing the impact of a reasonably likely surrogate endpoint on long-term graft survival in prospective kidney transplant clinical trials, TTC established a real-world evidence workgroup evaluating the scientific value of using transplant registry data as external control to supplement internal control group. UNOS retrospectively simulated the use of several distinct contemporaneous external control groups, applied multiple cause inference methods, and compared treatment effects to those observed in the BENEFIT study...

Solid organ transplant donor-recipient eplet mismatch has been correlated with donor-specific antibody (DSA) formation, antibody-mediated rejection, and overall rejection rates. However, studies have been predominantly in patients on tacrolimus-based immunosuppression regimens and have not fully explored differences in ethnically and racially diverse populations. Evidence indicates that patients on belatacept have lower rates of DSA formation, suggesting mediation of the immunogenicity of mismatched human leukocyte antigen polymorphisms...

Immunosuppressive agents are used post-organ transplant to prevent acute rejection and graft losses. Tacrolimus, the most widely used immunosuppressive agent for kidney transplant recipients, has unfavorable side effects such as new-onset diabetes after transplant, nephrotoxicity, and electrolyte imbalances. Other drug groups such as the mammalian target of rapamycin (mTOR) inhibitors, belatacept, and bleselumab have been used to either substitute calcineurin inhibitors or reduce their exposure. This systematic analysis reviews evidence from randomized controlled trials to compare the safety and efficacy of various immunosuppressive regimens for kidney transplant recipients...

The humoral response mediated by alloantibodies directed against donor HLA molecules (DSAs) is one of the main causes of graft loss in kidney transplantation. Understanding the pathophysiology leading to humoral kidney rejection as the development of therapeutic tools is therefore a main objective in the field of solid organ transplantation and necessitate adapted experimental models. Among the immunosuppressive agents used in renal transplantation, belatacept, a fusion protein targeting T costimulatory molecules has shown its ability to prevent more efficiently the secretion of DSA by different mechanisms including a direct action on plasma cells but also on B lymphocytes and follicular helper T lymphocytes (Tfh) cooperation...

The first COVID-19 stay-at-home order came into effect in France on 17 March 2020. Immunocompromised patients were asked to isolate themselves, and outpatient clinic visits were dramatically reduced. In order to avoid visits to the hospital by belatacept-treated kidney transplant recipients (KTRs) during the initial period of the pandemic, we promptly converted 176 KTRs at two French transplant centers from once-monthly 5 mg/kg in-hospital belatacept infusion to once-weekly 125 mg subcutaneous abatacept injection...