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

2019 ◽  
Vol 12 (4) ◽  
pp. 592-599 ◽  
Author(s):  
Hatem Ali ◽  
Atif Mohiuddin ◽  
Ajay Sharma ◽  
Ihab Shaheen ◽  
Jon Jin Kim ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Graft Survival ◽  
Induction Therapy ◽  
Meta Analysis ◽  
Interleukin 2 ◽  
Forest Plot ◽  
Renal Transplant Recipients ◽  
Number Of Patients ◽  
Antibody Induction ◽  
Standard Risk

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.

MO981OUTCOMES OF INTERLEUKIN-2 RECEPTOR ANTAGONIST INDUCTION THERAPY IN STANDARD-RISK RENAL TRANSPLANT RECIPIENTS MAINTAINED ON TACROLIMUS - A SYSTEMATIC REVIEW AND META-ANALYSIS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Hatem Kaies Ibrahim Elsayed Ali ◽  
Mahmoud Mohamed ◽  
Ajay Sharma ◽  
Tibor Fulop ◽  
Ahmed Halawa
Keyword(s):  
Renal Transplant ◽  
Graft Survival ◽  
Risk Ratio ◽  
Induction Therapy ◽  
Meta Analysis ◽  
Graft Function ◽  
Delayed Graft Function ◽  
Renal Transplant Recipients ◽  
Number Of Patients ◽  
Standard Risk

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 <5 and PRA<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.

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

2020 ◽  
Vol 51 (5) ◽  
pp. 366-372
Author(s):  
Hatem Ali ◽  
Ajay Sharma ◽  
Ahmed Halawa
Keyword(s):  
Renal Transplant ◽  
Induction Therapy ◽  
Interleukin 2 ◽  
Receptor Blocker ◽  
Post Transplant ◽  
Transplant Patients ◽  
Induction Group ◽  
Significant Difference ◽  
Renal Transplant Patients ◽  
Standard Risk

Background: This study aims to assess outcomes of interleukin-2 (IL-2) receptor blocker induction therapy on allograft and patients’ outcomes in standard risk recipients in the tacrolimus era, analysing data form the British Renal Transplant Registry. Methods: The study population involved all standard-risk renal transplant patients from 2000 till 2015 who were registered in the UK transplant registry and followed up till May 2018. Standard risk transplants were defined as patients with <2DR mismatch, calculated reaction frequency <20%, live donors or donors after brain death and patients with no previous renal transplantation transplant. We used inverse probability weights to adjust different covariates between the groups. Cox regression analysis for adjusted data and treatment effects model were used to assess outcomes. Results: In all, 3,597 renal transplant patients were included in the study. Two groups were identified; induction group (n = 2,858) which included patients who received IL-2 receptor blocker induction therapy and the no-induction group (n = 739). There was no significant difference between both groups in terms of estimated glomerular filtration rate (eGFR) rate at 1-year post-transplant (correlation co-efficient = 1.224, 95% CI ranges from –0.347 to 2.796). Average eGFR was 59.922 mL/min/1.73 m2 in the induction group (SD 29.171) and 64.557 mL/min/1.73 m2 in the no-induction groups (SD 46.763). There was no significant difference between both groups regarding graft survival at 5 years post-transplant (hazard ratio [HR] 0.944, 95% CI ranges from 0.599 to 1.485, p = 0.804), patient survival at 5 years post-transplant (HR 0.809, 95% CI ranges from 0.477 to1.372, p = 0.433). Conclusion: In the standard risk renal transplant population, the IL2 receptor blocker induction regimen does not affect eGFR at 1 year or renal and graft outcomes at 5 years.

MO980OUTCOMES OF RABBIT ANTI-THYMOCYTE GLOBULIN VERSUS IL-2 RECEPTOR ANTAGONIST INDUCTION THERAPIES IN 2DR MISMATCH RENAL TRANSPLANT RECIPIENTS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Hatem Kaies Ibrahim Elsayed Ali ◽  
Mahmoud Mohamed ◽  
Nithya Krishnan ◽  
Shafi Malik
Keyword(s):  
Renal Transplant ◽  
Acute Rejection ◽  
Graft Survival ◽  
Induction Therapy ◽  
Regression Models ◽  
Renal Transplant Recipients ◽  
Antigen Level ◽  
Transplant Recipients ◽  
Maintenance Immunosuppression ◽  
Significant Difference

Abstract Background and Aims 2DR HLA mismatch indicates high immunological risk renal transplant. Induction therapy with rabbit Anti-thymocyte Globulin (r-ATG) and IL-2 Receptor Antagonist (IL-2RA) resulted in marked reduction of acute allograft rejection rate and improved graft survival. However, the outcomes in 2DR (HLA-DR) mismatched renal transplant recipients (RTRs) in the era tacrolimus-mycophenolate mofetil maintenance immunosuppression remains understudied. Method This was a retrospective cohort study using data from the United States Organ Procurement and Transplantation Network, all 2 DR mismatched RTRs who were maintained on tacrolimus and mycophenolate mofetil immunotherapy between 2005 and 2015 were included. Follow up data was until September 2020. Patients who received transplants from living donors were included in the study. Collected data included recipient factors (age, sex, ethnicity, diabetes, body mass index), transplant factors (delayed graft function, cold ischemia time, number of previous transplants, panel reactive antibodies, HLA-mismatches, induction therapies, maintenance immunotherapy, and donor factors (donor type, donor age). RTRs were divided into 2 groups: based on induction therapy r-ATG and IL-2RA. Instrumental variable regression models were used to assess effect of induction therapy on acute rejection episodes at 6 months post-transplant and on graft survival. Type of induction therapy was instrumented for the transplant centre to reduce the centre effect on the choice of the induction therapy. Cox proportional hazard regression analysis was performed to assess the effect of induction therapy on graft survival. The regression models were adjusted for collected recipient, donor and transplant factors. Results 3052 patients received IL2-RA while 5143 patients received R-ATG induction. Using instrumental variables regression models, there were no significant differences between IL2-RA versus R-ATG induction in acute rejection episodes (OR=1.49, 95% CI ranges from 0.73 to 3.05, P=0.27), or graft survival (coefficient=0.95, 95% CI: -0.18 to 2.10, P=0.10). Using Cox proportional hazards regression, there was no significant difference in graft survival between either induction therapies (HR=0.90, 95% CI: 0.74 to 1.09, P=0.29). Conclusion This study showed no significant difference in acute rejection episodes or graft survival when using ATG or IL-2RA in 2DR HLA mismatched renal transplant recipients in the current tacrolimus-based maintenance immunosuppression era. Therefore, IL2-RA is a safe induction therapy in this group of patients and non-inferior to R–ATG induction therapy. Moreover, this study also highlights the fact that antigen level 2DR mismatches are not a risk factor for rejection and HLA matching should be based on epitope level rather than antigen level.

scholarly journals MO012IS IT SAFE TO USE INTERLEUKIN-2 RECEPTOR ANTAGONIST INDUCTION THERAPY IN 2DR MISMATCH RENAL TRANSPLANTS IN TACROLIMUS ERA?

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Hatem Kaies Ibrahim Elsayed Ali ◽  
Ahmed Daoud ◽  
Mahmoud Mohamed ◽  
Karim Soliman
Keyword(s):  
Regression Analysis ◽  
Mycophenolate Mofetil ◽  
Renal Transplant ◽  
Acute Rejection ◽  
Receptor Antagonist ◽  
Graft Survival ◽  
Induction Therapy ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Maintenance Immunosuppression

Abstract Background and Aims 2DR HLA mismatch indicates high immunological risk renal transplant. Induction therapy with rabbit Anti-thymocyte Globulin (r-ATG) and IL-2 Receptor Antagonist (IL-2RA) resulted in marked reduction of acute allograft rejection rate and improved graft survival. However, the outcomes in 2DR (HLA-DR) mismatched renal transplant recipients (RTRs) in the era tacrolimus-mycophenolate mofetil maintenance immunosuppression remains understudied. Method Using data from the United States organ procurement and transplantation network, all 2 DR mismatched RTRs with panel reactive antibodies &lt;20% maintained on tacrolimus and mycophenolate mofetil immunotherapy between 2000 and 2017 were retrospectively reviewed. Data including age, sex, gender, ethnicity, functional status, diabetes, body mass index, cold ischemia time, number of previous transplants, panel reactive antibodies, donor type, donor age, HLA-mismatches, number of acute rejection episodes, induction therapies, maintenance immunotherapy, recipients and graft survival were collected. Based on induction therapies administered, RTRs were divided into 2 groups: (r-ATG) and IL-2RA groups. Poisson regression analysis was used to assess effect of induction therapies on acute rejection episodes. Cox hazard regression analysis was used to assess effect of different induction therapies on patient and graft survival Results 3379 patients received IL2-RA while 3677 patients received ATG for induction. There were no significant differences between both groups in terms of acute rejection episodes (95% CI ranges from 0.95 to 1.068, P=0.805), graft survival (95% CI: 0.91 - 1.06, P=0.712), or patient survival (95% CI: -0.949 - 1.12, P=0.43) . Conclusion This study revealed no significant difference in acute rejection episodes, patient or graft survival when utilizing ATG vs IL-2RA in 2DR HLA mismatched renal transplant recipients with PRA&lt;20%, in the tacrolimus-based maintenance immunosuppression era. Therefore, IL2-RA is a safe induction therapy in this group of patients and non-inferior to –ATG induction therapy.

Interleukin 2 receptor antagonists for renal transplant recipients: a meta-analysis of randomized trials1

2004 ◽  
Vol 77 (2) ◽  
pp. 166-176 ◽  
Author(s):  
Angela C. Webster ◽  
E. Geoffrey Playford ◽  
Gail Higgins ◽  
Jeremy R. Chapman ◽  
Jonathan C. Craig
Keyword(s):  
Renal Transplant ◽  
Meta Analysis ◽  
Interleukin 2 ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Receptor Antagonists ◽  
Interleukin 2 Receptor

scholarly journals Steroid-free immunosuppression in cyclosporine-treated renal transplant recipients: a meta-analysis.

1993 ◽  
Vol 4 (6) ◽  
pp. 1300-1305
Author(s):  
D E Hricik ◽  
M A O'Toole ◽  
J A Schulak ◽  
J Herson
Keyword(s):  
Renal Transplant ◽  
Graft Survival ◽  
Steroid Therapy ◽  
Allograft Rejection ◽  
Meta Analysis ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Acute Allograft Rejection ◽  
Maintenance Immunosuppression ◽  
Prospective Trials

Data from seven randomized, prospective trials were pooled to determine the effect of steroid-free immunosuppression on allograft survival, patient survival, and the incidence of acute allograft rejection in renal transplant recipients receiving cyclosporine-based maintenance immunosuppression. Six of the seven trials incorporated into this analysis examined the effects of either complete avoidance of steroids or withdrawal of steroids less than 3 months after transplantation. Only one of the studies estimated patient and graft survival beyond 2 yr. Results of the meta-analysis suggest that avoiding steroid therapy from the time of transplantation or withdrawing steroid therapy at some time after transplantation increases the risk of acute allograft rejection without adversely affecting patient or graft survival. However, these results may not accurately reflect the risk of acute allograft rejection in patients subjected to later withdrawal of steroids. Longer periods of follow-up are required to assess the risk of chronic rejection in cyclosporine-treated renal transplant recipients who are not receiving steroids.

scholarly journals SaO013SIGNIFICANCE OF INDUCTION THERAPY WITH IL-2 RECEPTOR ANTAGONIST IN STANDARD-RISK RENAL TRANSPLANT IN TACROLIMUS ERA: A META-ANALYSIS

2018 ◽  
Vol 33 (suppl_1) ◽  
pp. i320-i321
Author(s):  
Hatem Ali ◽  
Atif Mohiuddin ◽  
Ajay Sharma ◽  
Mohsen El Kosi ◽  
Ahmed Halawa
Keyword(s):  
Renal Transplant ◽  
Receptor Antagonist ◽  
Induction Therapy ◽  
Meta Analysis ◽  
Standard Risk

Outcomes of Interleukin-2 Receptor Antagonist Induction Therapy in Standard-Risk Renal Transplant Recipients Maintained on Tacrolimus: A Systematic Review and Meta-Analysis

2021 ◽  
pp. 1-13
Author(s):  
Hatem Ali ◽  
Mahmoud M. Mohamed ◽  
Ajay Sharma ◽  
Tibor Fulop ◽  
Ahmed Halawa
Keyword(s):  
Acute Rejection ◽  
Risk Ratio ◽  
Induction Therapy ◽  
Meta Analysis ◽  
Interleukin 2 ◽  
Transplant Recipients ◽  
Group A ◽  
Group B ◽  
Standard Risk ◽  
Rejection Rates

<b><i>Introduction:</i></b> The additive benefit of interleukin-2 receptor antagonist (IL2-RA) induction in standard-risk kidney transplant recipients, while maintained on tacrolimus-based immunosuppressive therapy, is uncertain. <b><i>Methods:</i></b> We divided the studies included in this meta-analysis into 2 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 vs. those who received no-induction therapy and high dose of tacrolimus). <b><i>Results:</i></b> In group A, 11 studies were included (<i>n</i> = 2,886). IL2-RA induction therapy was not associated with significant differences in comparison to no-induction therapy in terms of acute rejection rates at 6 months post-transplant (risk ratio = 1.12 and 95% confidence interval [CI] range: 0.94–1.35) or graft survival at 1 year post-transplant (risk ratio = 0.78 and 95% CI range: 0.45–1.36). In group B, 2 studies were included (<i>n</i> = 669). There was no difference between both arms in terms of acute rejection rates (risk ratio = 0.62, with 95% CI range: 0.33–1.14) or graft survival (risk ratio = 1 and 95% CI range: 0.57–1.74). <b><i>Conclusion:</i></b> IL2-RA induction therapy does not improve outcomes in patients maintained on tacrolimus-based immunotherapy in standard-risk population.

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