Interleukin 2 receptor antagonists for kidney transplant recipients

Webster, Angela C; Playford, E. Geoffrey; Higgins, Gail; Chapman, Jeremy R.; Craig, Jonathan C.

doi:10.1002/14651858.cd003897.pub2

Cited by 73 publications

(83 citation statements)

References 71 publications

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“…In contrast to the benefits among high immunologic risk patients, the benefits of TMG in lower immunologic risk patients are less clear. A 2009 Cochrane meta‐analysis examined 71 randomized clinical trials comparing different induction therapy . The reviewed trials dominantly enrolled low immunological risk recipients, with 72% being first‐time transplant recipients.…”

Section: Discussionmentioning

confidence: 99%

Center practice drives variation in choice of US kidney transplant induction therapy: a retrospective analysis of contemporary practice

et al. 2017

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To assess factors that influence the choice of induction regimen in contemporary kidney transplantation, we examined center-identified, national transplant registry data for 166 776 US recipients (2005-2014). Bilevel hierarchical models were constructed, wherein use of each regimen was compared pairwise with use of interleukin-2 receptor blocking antibodies (IL2rAb). Overall, 82% of patients received induction, including thymoglobulin (TMG, 46%), IL2rAb (22%), alemtuzumab (ALEM, 13%), and other agents (1%). However, proportions of patients receiving induction varied widely across centers (0-100%). Recipients of living donor transplants and self-pay patients were less likely to receive induction treatment. Clinical factors associated with use of TMG or ALEM (vs. IL2rAb) included age, black race, sensitization, retransplant status, nonstandard deceased donor, and delayed graft function. However, these characteristics explained only 10-33% of observed variation. Based on intraclass correlation analysis, "center effect" explained most of the variation in TMG (58%), ALEM (66%), other (51%), and no induction (58%) use. Median odds ratios generated from case-factor adjusted models (7.66-11.19) also supported large differences in the likelihood of induction choices between centers. The wide variation in induction therapy choice across US transplant centers is not dominantly explained by differences in patient or donor characteristics; rather, it reflects center choice and practice.

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Section: Discussionmentioning

confidence: 99%

Center practice drives variation in choice of US kidney transplant induction therapy: a retrospective analysis of contemporary practice

et al. 2017

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“…A series of trials has demonstrated that induction therapy with ATG or IL2RA induction reduces the risk of early acute rejection episodes after kidney transplantation versus controls . In 2010, the Cochrane Collaboration published a meta‐analysis of randomized controlled trials that compared IL2RA induction with placebo and with ATG . Biopsy‐proven acute rejection (BPAR) rates were ≈30% lower with IL2RA versus placebo (1‐year relative risk [RR] 0.72, 95% confidence interval [CI] 0.64–0.81) and graft loss was reduced (1‐year RR 0.75, 95% CI 0.62–0.90]).…”

Section: Introductionmentioning

confidence: 99%

Induction Therapy for Kidney Transplant Recipients: Do We Still Need Anti-IL2 Receptor Monoclonal Antibodies?

Hellemans

Bosmans

Abramowicz

2017

American Journal of Transplantation

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Induction therapy with antilymphocyte biological agents is widely used after kidney transplantation, most commonly T lymphocyte‐depleting rabbit‐derived antithymocyte globulin (rATG) or an IL‐2 receptor antagonist (IL2RA). Early randomized trials showed that rATG or IL2RA induction reduces early acute rejection, prompting recommendations by Kidney Disease Improving Global Outcomes that IL2RA induction be used routinely in first‐line therapy after kidney transplantation, with lymphocyte‐depleting induction reserved for high‐risk cases. These studies, however, mainly used outdated maintenance regimens. No large randomized trial has examined the effect of IL2RA or rATG induction versus no induction in patients receiving tacrolimus, mycophenolic acid and steroids. With this triple maintenance therapy, the addition of induction may achieve an absolute risk reduction for acute rejection of only 1–4% in standard‐risk patients without improving graft or patient survival. In contrast, rATG induction lowers the relative risk of acute rejection by almost 50% versus IL2RA in patients with high immunological risk. These recent data raise questions about the need for IL2RA in kidney transplantation, as it may no longer be beneficial in standard‐risk transplantation and may be inferior to rATG in high‐risk situations. Updated evidence‐based guidelines are necessary to support clinicians deciding whether and what induction therapy is required for their transplant patients today.

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“…We observed substantially more BPAR within 6 months in patients treated primarily with CyA compared with the study group, which is probably related to the fact that induction therapy was not standard of practice at our center at that time . The rejection rate in the belatacept group was lower than the range observed in the BENEFIT trial (17–22%), but higher than the ones seen in the phase II trial (6–7%).…”

Section: Discussionmentioning

confidence: 55%

Long-term outcome of belatacept therapy in de novo kidney transplant recipients - a case-match analysis

et al. 2015

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Conflicts of interest TW has received research grants, travel support, and honoraria from Bristol-Myers Squibb. FM received honoraria from BristolMyers Squibb. CS has received travel grants and speaker fees from Bristol-Myers Squibb. SM has received travel grants from BristolMyers Squibb. BW received honoraria from Bristol-Myers Squibb. SummaryWhile belatacept has shown favorable short-and midterm results in kidney transplant recipients, only projections exist regarding its potential impact on long-term outcome. Therefore, we performed a retrospective case-match analysis of the 14 belatacept patients originally enrolled in the phase II multicenter trial at our center. Fifty six cyclosporine (CyA)-treated patients were matched according to age at transplantation, first/retransplant, and donor type. Ten years after kidney transplantation, kidney function remained superior in belatacept-treated patients compared with the CyA control group. Moreover, none of the belatacept-treated patients had donor-specific antibodies ≥10 years post-transplantation compared with 38.5% of tested CyA-treated subject (0/10 vs. 5/13; P = 0.045). Notably, however, patient and graft survival was virtually identical in both groups (71.4% vs. 71.3%; P = 0.976). In the present single-center study population, patients treated with belatacept demonstrated a patient and graft survival at 10 years posttransplant which was comparable to that of similarly selected CNI-treated patients. Larger studies with sufficient statistical power are necessary to definitively determine long-term graft survival with belatacept.

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Interleukin 2 receptor antagonists for kidney transplant recipients

Cited by 73 publications

References 71 publications

Center practice drives variation in choice of US kidney transplant induction therapy: a retrospective analysis of contemporary practice

Center practice drives variation in choice of US kidney transplant induction therapy: a retrospective analysis of contemporary practice

Induction Therapy for Kidney Transplant Recipients: Do We Still Need Anti-IL2 Receptor Monoclonal Antibodies?

Long-term outcome of belatacept therapy in de novo kidney transplant recipients - a case-match analysis

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