MO981OUTCOMES OF INTERLEUKIN-2 RECEPTOR ANTAGONIST INDUCTION THERAPY IN STANDARD-RISK RENAL TRANSPLANT RECIPIENTS MAINTAINED ON TACROLIMUS - A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Ali Hatem Kaies Ibrahim Elsayed , Mohamed Mahmoud , Sharma Ajay , Fulop Tibor , Halawa Ahmed 
Published: May 2021

Abstract

Background and Aims
Interleukin-2 (IL-2) antagonist has been used as an induction therapy in many centres in calcineurin inhibitor-sparing regimens. Tacrolimus has overwhelmingly replaced cyclosporine in the maintenance immunosuppressive protocols in many transplant centres. The aim of our study and meta-analysis is to explore the effect of IL-2 induction therapy on the rate of rejection and patient and graft survival in standard-risk renal transplant patients with tacrolimus-based maintenance immunotherapy. Secondary aims included assessment of the effect of IL-2 induction therapy on the risk of delayed graft function, cytomegalovirus (CMV) infection, and malignancy.

Method
We conducted a systematic review in different databases to identify studies and research work that assessed the effect of IL-2 antibody induction therapy on renal transplant outcomes. Inclusion criteria for our meta-analysis were all studies that compared IL-2 induction therapy with placebo or no induction therapy in standard-risk renal transplant recipients on tacrolimus-based maintenance immunosuppressive therapy. Data collected were the name of the first author, journal title, year of publication, country where the study was conducted, number of patients in the IL-2 induction therapy arm and in the placebo arm, number of patients who had biopsy-proven rejection and graft survival in each arm. A random effects model was used for the meta-analysis. We divided the studies included in this meta-analysis into two groups: Group A (included studies that used same dose of tacrolimus in both arms of each study) and Group B (included studies that compared patients who received induction therapy and low dose tacrolimus versus those who received no induction therapy and high dose of tacrolimus). Standard-risk renal transplant was defined as HLA mismatch &lt;5 and PRA&lt;50%.

Results
In group A, 11 studies were included (n=2886). IL2-RA induction therapy was not associated with significant differences in comparison to no induction therapy in terms of acute rejection rates (Risk Ratio=1.03, 95% Confidence Interval [CI] range: 0.84 - 1.26, I squared=0%, P=0.79), graft survival (Risk Ratio=1.15, 95% CI range: 0.82 to 1.62), delayed graft function (Risk Ratio=1.01, 95% CI range: 0.82 to 1.24), CMV infection (Risk Ratio =1.37, 95% CI range: 0.53 to 3.51) or malignancy (Risk Ratio=1.29, 95% CI range: 0.61 to 2.75). In group B, two studies were included (n=669). There was no difference between both arms in terms of acute rejection rates (Risk Ratio=0.62, with 95% CI range: 0.33 to 1.14) or graft survival (Risk Ratio=1, 95% CI range: 0.57 to 1.74) or delayed graft function (Risk Ratio=0.88, 95% CI range: 0.45 to 1.71).

Conclusion
IL2-RA induction therapy does not improve outcomes in patients maintained on tacrolimus-based immunotherapy in standard risk population. our results strengthen the argument for individualized medical therapy and the potential tailoring the immunosuppression regimes according to the actual patients, needs.