Interleukin-2 Receptor Antagonists as Induction Therapy After Heart Transplantation: Systematic Review With Meta-Analysis of Randomized Trials

Møller, Cleide Oliveira de Almeida; Gustafsson, Finn; Gluud, Christian; Steinbrüchel, Daniel A.

doi:10.1016/j.healun.2008.05.013

Cited by 24 publications

(22 citation statements)

References 27 publications

(37 reference statements)

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“…Rejection therapy with lymphocyte‐depleting agents in patients receiving IL‐2RA induction appears to result in over‐immunosuppression and should be avoided. Overall, however, the rate of infection or CMV infection does not appear to be affected by use of IL‐2RA induction following heart transplantation, as confirmed by a recent meta‐analysis .…”

Section: Safety Concernsmentioning

confidence: 67%

Induction therapy in heart transplantation: where are we now?

et al. 2013

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Summary Although induction therapy has been used in heart transplantation for many years, its role has not been fully elucidated. Early safety concerns relating to OKT3 or intensive lymphocyte‐depleting regimens have largely been addressed by modern induction protocols using rabbit antithymocyte globulin (rATG [Thymoglobuline® or ATG‐Fresenius]) and interleukin‐2 receptor antagonist (IL‐2RA) agents, but although the number of randomized controlled studies has expanded there are still gaps in the evidence base. Rejection prophylaxis may be somewhat more effective with rATG than IL‐2RA agents, but this has not been proven conclusively. Administration of induction therapy to support delayed introduction of calcineurin inhibitors in patients at risk of renal dysfunction is relatively well documented and widely used. Increasingly, it is recognized that sensitized patients and individuals with primary graft function are suitable candidates for induction therapy, and the possibility that rATG may inhibit cardiac allograft vasculopathy is also of considerable interest. Until the question of whether rATG is associated with increased risk of infection, routine prophylaxis is advisable. IL‐2RA induction has an excellent safety profile. Dosing rATG according to lymphocyte count reduces cumulative dose without compromising efficacy. Further controlled trials are required to determine when and how to deploy induction most effectively following heart transplantation.

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Section: Safety Concernsmentioning

confidence: 67%

Induction therapy in heart transplantation: where are we now?

et al. 2013

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“…[4] A meta-analysis of adult heart transplant recipients who underwent induction therapy with IL-2 receptor antagonists found no convincing evidence of a survival benefit or reduction in rejection with their use. [15] Data from the 2007 ISHLT pediatric registry reported no significant effect of induction therapy on coronary artery graft vasculopathy; this was not readdressed in the 2010 report. [2,4] Renal dysfunction is a common morbidity pre-and postheart transplant.…”

Section: Rationalementioning

confidence: 98%

Strategies to Prevent Cellular Rejection in Pediatric Heart Transplant Recipients

Denfield

2010

Pediatric Drugs

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Despite more than 40 years' experience in pediatric heart transplantation, cellular rejection remains a significant cause of morbidity and mortality. In this review, strategies and agents to prevent acute cellular rejection are discussed. Strategies to prevent rejection are divided into two phases - induction and maintenance therapies. Currently, the most commonly used induction agents are polyclonal antibodies (rabbit or equine antithymocyte globulin) and interleukin-2 receptor antibodies (daclizumab or basiliximab). Induction therapies have reduced early rejection, are renal sparing, and can reduce corticosteroid exposure, but have not yet been shown to have a longer term survival benefit. Multiple maintenance immunosuppressants are available. Nearly all regimens include a calcineurin inhibitor (either ciclosporin [cyclosporine] or tacrolimus). Most combinations in pediatric heart transplantation include an antiproliferative agent (azathioprine, mycophenolate mofetil or, less commonly, sirolimus). Everolimus has seen increasing use in adult heart transplant patients in Europe but, to date, its use is rare in pediatric heart transplantation. The use of corticosteroids as a third agent is still common, but strategies to avoid or minimize their use are increasing. The 'best' combination of therapies varies between studies. By gaining a better understanding of individuals' genetic and environmental risk factors, we may in the future be able to better predict the course of cardiac allografts and enhance our ability to tailor immunosuppression to individual patient variables with the ultimate goal of inducing a state of immune tolerance.

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“…Only one trial showed more cases of CMV conversion detected by PCR during the first 3 months [22]. A meta-analysis of all randomized trials of IL-2 receptor antagonists showed no differences in overall infection as well as CMV infection compared with placebo, polyclonal, or OKT3 induction [31]. Teuteberg et al [27 ] describes lower CMV rates with alemtuzumab induction during the first 6 months after transplantation (8.3 vs. 19.4%; P ¼ 0.02).…”

Section: Infectionmentioning

confidence: 98%