Belatacept-Based Immunosuppression in De Novo Liver Transplant Recipients: 1-Year Experience From a Phase II Randomized Study

Abstract

This exploratory phase II study evaluated the safety and efficacy of belatacept in de novo adult liver transplant recipients. Patients were randomized (N = 260) to one of the following immunosuppressive regimens: (i) basiliximab + belatacept high dose [HD] + mycophenolate mofetil (MMF), (ii) belatacept HD + MMF, (iii) belatacept low dose [LD] + MMF, (iv) tacrolimus + MMF, or (v) tacrolimus alone. All received corticosteroids. Demographic characteristics were similar among groups. The proportion of patients who met the primary end point (composite of acute rejection, graft loss, death by month 6) was higher in the belatacept groups (42–48%) versus tacrolimus groups (15–38%), with the highest number of deaths and grafts losses in the belatacept LD group. By month 12, the proportion surviving with a functioning graft was higher with tacrolimus + MMF (93%) and lower with belatacept LD (67%) versus other groups (90%: basiliximab + belatacept HD; 83%: belatacept HD; 88%: tacrolimus). Mean calculated GFR was 15–34 mL/min higher in belatacept-treated patients at 1 year. Two cases of posttransplant lymphoproliferative disease and one case of progressive multifocal leukoencephalopathy occurred in belatacept-treated patients. Follow-up beyond month 12 revealed an increase in death and graft loss in another belatacept group (belatacept HD), after which the study was terminated.

Immunomodulatory Effects of Fentanyl or Dexmedetomidine Hydrochloride Infusion After Allogeneic Heart Transplantation in Mice

“…13 Homeostasis and immune milieu of transplant recipients change following allogeneic transplantation due to immunosuppressive regimens that may include calcineurin inhibitors, mycophenolic acid, steroids, rapamycin, and anti-T-or B-cell antibodies. [15][16][17][18][19][20] Despite often critical conditions in the peritransplant period due to end-stage organ failure, high-dose immunosuppression is required in the induction period to avoid early sensitization. [20][21][22] The induction treatment is therefore crucial to maintain an appropriate immune balance to avoid both rejection and infection.…”

CD28 Costimulation: From Mechanism to Therapy

“…A clinical trial to further investigate abatacept efficacy in lupus nephritis is ongoing. Belatacept treatment was associated with increased graft loss and death in liver transplant patients (Klintmalm et al, 2014). Abatacept does not improve respiratory function in patients with mild asthma (Parulekar et al, 2013).…”

Impact of Immune-Modulatory Drugs on Regulatory T Cell

“…Long-term clinical follow-up of kidney transplant patients treated with belatacept demonstrates superior graft function at 5 years without differences in graft or patient survival when compared to CNI-based immunosuppression 162,163 . Studies in liver transplantation are less encouraging 164 and CTLA4-Ig has not been well studied in other solid organ transplants. Overall, CTLA4-Ig is compatible with Treg function at the right dose and can be an effective replacement for CNI at thwarting rejection with minimal renal toxicity.…”