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Everolimus and Long-term Clinical Outcomes in Kidney Transplant Recipients

A Registry-based 10-year Follow-up of 5 Randomized Trials

Ying, Tracey FRACP1; Wong, Germaine FRACP, PhD2; Lim, Wai H. PhD3; Clayton, Philip FRACP, PhD4; Kanellis, John PhD, FRACP5; Pilmore, Helen MD, FRACP6,7; Campbell, Scott FRACP, PhD8; O’Connell, Philip J. FRACP, PhD9; Russ, Graeme FRACP, PhD10; Chadban, Steven FRACP, PhD11,12

doi: 10.1097/TP.0000000000002499
Original Clinical Science—General
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Background. Data regarding the long-term efficacy of everolimus-based immunosuppression for kidney transplantation are lacking. Existing randomized controlled trials are limited by short follow-up duration which limits capacity to assess impact on graft and patient survival.

Methods. We linked individual trial participants to the Australian and New Zealand Dialysis and Transplant Registry. Using a 1-step meta-analysis approach, we investigated the 10-year risk of graft loss, mortality and graft function in 349 participants from 5 randomized trials of everolimus-based immunosuppression.

Results. Two hundred forty-two patients randomized to everolimus and 107 control patients were followed for a median of 9 years (interquartile range, 7.1, 9.8 y). There were no significant differences in the risk of all-cause graft loss (adjusted hazard ratio [HR], 1.16; 95% confidence interval [CI], 0.69-1.94), mortality (adjusted HR, 1.51; 95% CI, 0.78-2.93) and death-censored graft loss in everolimus versus control (adjusted HR, 1.00; 95% CI, 0.50-2.01). For patients in the early initiation (de novo or <6-month conversion) everolimus trials (n = 279), decline in estimated glomerular filtration rate did not significantly differ with control (mean difference in the slope of estimated glomerular filtrate rate, 0.01 mL/min per 1.73 m2 [−0.06 to +0.09]).

Conclusions. This registry-based analysis with long-term follow-up found no differences in graft and recipient survival or graft function for everolimus over current standard of care.

1 Renal Medicine, Royal Prince Alfred Hospital, Kidney Node at Charles Perkins Centre, Sydney Medical School, University of Sydney, Camperdown, NSW, Australia.

2 Centre for Transplant and Renal Research, Westmead Hospital, Centre for Kidney Research, The Children’s Hospital at Westmead, NSW, Australia.

3 Department of Renal Medicine, Sir Charles Gairdner Hospital, School of Medicine, University of Western Australia, Perth, Australia.

4 Central and Northern Adelaide Renal and Transplantation Services, South Australia, Australia.

5 Department of Nephrology, Monash Health, Clayton, Centre for Inflammatory Diseases Department of Medicine, Monash University, Melbourne, VIC, Australia.

6 Department of Renal Medicine, Auckland City Hospital, Auckland, New Zealand.

7 Department of Medicine, Auckland University, Auckland, New Zealand.

8 Department of Renal Medicine, University of Queensland at Princess Alexandria Hospital, Woolloongabba, QLD, Australia.

9 Department of Renal Medicine, Westmead Hospital, Westmead, NSW, Australia.

10 Central and Northern Adelaide Renal and Transplantation Services, South Australia, Australia.

11 Renal Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.

12 Kidney Node at Charles Perkins Centre, Sydney Medical School, University of Sydney, Camperdown, NSW, Australia.

Received 12 August 2018. Revision received 3 October 2018.

Accepted 12 October 2018.

W.L., J.K., S.C., R.W., P.O’C., G.R.R., and S.J.C. have served on the Australian Novartis Transplant Advisory Board and have received sponsorship (to institution) for trial conduct and/or international conference attendance.

T.Y. is funded by the Dr Pamela Guha Research Scholarship for her PhD.

T.Y. participated in research design, writing of the article, acquisition of data and data analysis. G.W. participated in research design, writing of the article and data analysis. W.L. participated in research design, writing of the article and data analysis. P.C. participated in research design, writing of the article and data analysis. J.K. participated in research design, writing of the article and performance of the original research. H.P. participated in research design, writing of the article and performance of the original research. S.C. participated in research design, writing of the article and performance of the original research. P.O’C. participated in research design, writing of the article and performance of the original research. G.R. participated in research design, writing of the article and performance of the original research. S.C. participated in research design, writing of the article, acquisition of data and data analysis.

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

Correspondence: Tracey Ying, FRACP, Renal Medicine, Royal Prince Alfred Hospital, Camperdown, Kidney Node at Charles Perkins Centre, Sydney Medical School, University of Sydney, Sydney, NSW, Australia. (tracey.ying@health.nsw.gov.au).

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