Belatacept in renal transplantation in comparison to tacrolimus and molecular understanding of resistance pattern: Meta-analysis and systematic review

BACKGROUND The T-cell costimulation blocking agent belatacept has been identified as a possible substitute for calcineurin inhibitors, however, no consensus has been established against its use over the standard care agent Tacrolimus. AIM To evaluate the effectiveness of belatacept based maintenance immunosuppressive regimens in comparison to tacrolimus in renal transplantion. METHODS We did extensive search of all the available literature comparing the role of belatacept to tacrolimus in renal transplant recipients by searching the PubMed, Embase, Cochrane, Crossref, Scopus, clinical trials registry on October 5, 2020. RESULTS The literature search identified four randomized controlled trials (n = 173 participants) comparing belatacept with tacrolimus. There was no significant difference in estimated renal function at 12 mo [mean difference 4.12 mL/min/1.73 m2, confidence interval (CI): -2.18 to 10.42, P = 0.20]. Further, belatacept group was associated with significant increase in biopsy proven acute rejection [relative risk (RR) = 3.27, CI: 0.88 to 12.11, P = 0.08] and worse 12 mo allograft survival (RR = 4.51, CI: 1.23 to 16.58, P = 0.02). However, incidence of new onset diabetes mellitus was lower with belatacept at 12 mo (RR = 0.26, CI: 0.07 to 0.99, P = 0.05). CONCLUSION The evidence reviewed in this meta-analysis suggested that belatacept-based maintenance immunosuppression regimens were associated with an increased risk allograft loss in renal transplant recipients with equivalent renal functioning against standard tacrolimus; however, observed significantly reduced new onset diabetes mellitus after transplantation incidence and lower serum low density lipid profile levels in belatacept group. In addition, the adaptation of belatacept in renal transplantation has been forestalled by increased rates of rejection and resistance owing to development of various effector memory T cells through, parallel differentiation and immunological plasticity