Implication of interleukin-2 receptor antibody induction therapy in standard risk renal transplant in the tacrolimus era: a meta-analysis

Abstract

Background 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 creatinine change and the risk of cytomegalovirus (CMV) infection. Methods 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. Results Of the 470 articles found in different databases, 7 were included in the meta-analysis. Forest plot analysis for rate of rejection during the follow-up period post-transplant showed no significant difference between the groups. There was no evidence of heterogenicity between included studies (I2 = 21.8%, P = 0.27). The overall risk difference was −0.02 [95% confidence interval (CI) −0.05–0.01]. A random effects meta-analysis for patient and graft survival was performed using forest plot analysis and showed no significant effect of IL-2 receptor (IL-2R) antibody induction on patient or graft survival compared with placebo. The overall risk difference was −0.01 (95% CI −0.04–0.01) and 0.00 (95% CI −0.00–0.01), respectively. Three of the included studies showed no effect of basiliximab on creatinine change, two showed no effect on risk of CMV infection and two showed less risk of post-transplant diabetes in the basiliximab group. Conclusion IL-2R antibody induction therapy has no significant effect on the rate of rejection or patient or graft survival in standard-risk renal transplant recipients on tacrolimus-based maintenance immunotherapy. More randomized controlled studies are needed.

Transplant Risk Assessment: It Is Not about the Panel Reactive Antibodies

“…We have read with great interest the article written by Ali et al [1] titled: “Outcomes of Interleukin-2 Receptor Antagonist Induction Therapy in Standard-Risk Renal Transplant Recipients Maintained on Tacrolimus: A Systematic Review and Meta-Analysis.” This meta-analysis included 12 RCTs and showed significant results and concluded that in standard-risk transplant patients maintained on tacrolimus and MMF, basiliximab induction therapy had no additional benefit compared to no-induction therapy. This conclusion was observed in previous retrospective studies [2, 3].…”

Induction Therapy, HLA Mismatching, and Standard-Risk Kidney Transplantation

“…The authors found no additive benefit for interleukin-2 induction therapy in the standard risk population. Similar results were shown in the previous registry and in retrospective studies [2, 3]. The authors used a broad definition for standard-risk renal transplant which included HLA mismatches of <5.…”

Effect of Interleukin-2 Receptor Antibody Induction Therapy on Survival in Renal Transplant Patients Receiving Tacrolimus

“…Several studies have been performed to assess the outcomes of IL-2 receptor antagonist induction therapy in standard risk population in tacrolimus era; most of these are retrospective studies with small sample size [10]. To the best of our knowledge, this is the first study to be performed in the United Kingdom.…”

“…The study population were restricted to standard risk patients who were maintained on tacrolimus-based immunotherapy. Standard risk transplants were defined as patients with < 2DR mismatch, calculated reaction frequency (CRF) < 20%, live donors or donors after brain death and patients with no previous renal transplantation [8,[10][11][12][13]. CRF is an indication of the level of sensitization and reflects the percentage of blood group identical, HLA incompatible donors [14].…”