Immunosuppression with Belatacept-Based, Corticosteroid-Avoiding Regimens in De Novo Kidney Transplant Recipients

Abstract

†Drs Ferguson and Grinyo contributed equally to the work described.Current immunosuppressive regimens in renal transplantation typically include calcineurin inhibitors (CNIs) and corticosteroids, both of which have toxicities that can impair recipient and allograft health. This 1-year, randomized, controlled, open-label, exploratory study assessed two belatacept-based regimens compared to a tacrolimus (TAC)-based, steroidavoiding regimen. Recipients of living and deceased donor renal allografts were randomized 1:1:1 to receive belatacept-mycophenolate mofetil (MMF), belataceptsirolimus (SRL), or TAC-MMF. All patients received induction with 4 doses of Thymoglobulin (6 mg/kg maximum) and an associated short course of corticosteroids. Eighty-nine patients were randomized and transplanted. Acute rejection occurred in 4, 1 and 1 patient in the belatacept-MMF, belatacept-SRL and TAC-MMF groups, respectively, by Month 6; most acute rejection occurred in the first 3 months. More than twothirds of patients in the belatacept groups remained on CNI-and steroid-free regimens at 12 months and the calculated glomerular filtration rate was 8-10 mL/min higher with either belatacept regimen than with TAC-MMF. Overall safety was comparable between groups. In conclusion, primary immunosuppression with belatacept may enable the simultaneous avoidance of both CNIs and corticosteroids in recipients of living and deceased standard criteria donor kidneys, with acceptable rates of acute rejection and improved renal function relative to a TAC-based regimen.

Chitinase-Like Protein Brp-39/YKL-40 Modulates the Renal Response to Ischemic Injury and Predicts Delayed Allograft Function

“…In addition, recent trials have demonstrated acceptable outcomes (with somewhat better long-term allograft function) for belataceptbased immunosuppressive regimens compared with calcineurin inhibitor-based therapy. 37,38 Trials designed to evaluate the efficacy of these and other calcineurin-sparing regimens could be planned in recipients identified as high risk for DGF based on urinary YKL-40 levels before or immediately after transplant.…”

Immunosuppressive therapy for kidney transplantation in adults: a systematic review and economic model

“…Only four induction studies [71][72][73][74] and six maintenance studies 58,[124][125][126][127]150 adequately addressed five or more of the 10 items of the quality appraisal assessment. However, even the reports of these trials omitted important information relating to quality, with six [71][72][73][74]124,125 of the seven failing to clearly describe the procedure used for allocation concealment, and one 58 failing to include an intention-to-treat (ITT) analysis.…”

“…The method of random allocation, 71,86,128 including the method of sequence generation, was clearly stated and adequate in only two induction studies 71,128 and 18 maintenance studies, 86,103,110,112,119,122,124,126,127,[129][130][131][132][133][134][135][136]150 whereas 65 studies (nine induction studies [72][73][74]87,95,98,137 and 54 maintenance studies 51,58,59,75-85,88,89,91-94,99-102, 104-109,111,113-118,120,121,125,138-147,152-155 ) and both of the studies of induction and maintenance treatment 123,148 did not clearly specify the method used. The remaining maintenance study 149 used a minimisation technique that included a random element.…”

“…Fifty-seven trials (48 maintenance studies, 51,58,77,[80][81][82]84,86,94,99,100,102,[104][105][106][107][108][109][113][114][115][116][117][119][120][121][124][125][126][127]131,132,134,138,139,[141][142][143][144][145][146][147]149,150,152,154,156,157 eight induction studies 71,72,74,87,97,128,137 and one study …”

Defining a Steroid Withdrawal Protocol in a newly established Kidney Transplantation Unit

“…After a 12 months study the biopsy proven AR rate for belatacept/MMF was 14%; for belatacept/sirolimus this fi gure was 4% and for control TAC/MMF this incidence was 3%. Steroid-free immunosuppression may, therefore, not be achieved through CNI-free protocols [61][62][63].…”