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Do long-term kidney transplant outcomes differ in patients treated with and without maintenance corticosteroids?
In a randomized clinical trial that allocated 385 patients to maintenance immunosuppressive treatment with tacrolimus and mycophenolate mofetil with or without corticosteroids, there was no difference in kidney allograft survival between treatment groups during the median follow-up of 15.8 years after transplant.
Corticosteroids may not be necessary as part of a calcineurin-based multiple drug immunosuppressive regimen in kidney transplant recipients.
The complications of corticosteroids make the inclusion of these drugs in immunosuppressive protocols for kidney transplant patients undesirable. However, cessation of corticosteroids is associated with a higher risk of short-term rejection, and the long-term outcomes of patients withdrawn from corticosteroids remain uncertain.
To compare long-term kidney transplant outcomes of patients randomized to continue or withdraw corticosteroids.
Design, Setting, and Participants
This prospective multicenter randomized double-blind placebo-controlled trial was conducted between November 1999 and December 2002 with linkage to a mandatory national registry with validated outcome ascertainment until June 8, 2018. The study included 28 kidney transplant centers in the United States, including 386 low– to moderate–immune risk adult recipients of a living or deceased donor kidney transplant without delayed graft function or short-term rejection in the first week after transplant. Analyses were intention to treat. Analysis began September 2018 and ended June 2019.
Patients were randomized to receive tacrolimus and mycophenolate mofetil with or without corticosteroids 7 days after transplant.
Main Outcomes and Measures
Kidney allograft failure from any cause including death and allograft failure censored for patient death defined by the requirement for long-term dialysis or repeat transplant.
Of 385 patients, 191 were assigned to withdraw from corticosteroids (mean [SD] age, 46.5 [12.1] years), and 194 patients were assigned to continued corticosteroids (mean [SD] age, 46.3 [12.6] years). The median (interquartile range) follow-up time was 15.8 (12.0-16.3) years after transplant. The adjusted hazard ratios of allograft failure from any cause including death was 0.83 (95% CI, 0.62-1.10; P = .19) and for allograft failure censored for patient death was 0.78 (95% CI, 0.52-1.19; P = .25) and did not differ between the patients assigned to withdraw from corticosteroids vs assigned to continued corticosteroids. Results were consistent in a per-protocol analysis among 223 patients who continued the trial-assigned treatment of corticosteroid withdrawal (n = 114) or corticosteroids (n = 109) through at least 5 years after transplant. The outcomes of trial participants in either treatment group did not differ from similarly treated contemporary registry patients who met trial eligibility criteria and were treated with the same immunosuppressive drugs.
Conclusions and Relevance
Long-term corticosteroids may not be necessary as part of a calcineurin-based multiple drug immunosuppressive regimen in low– to moderate–immune risk kidney transplant recipients.
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Corresponding Author: John S. Gill, MD, MS, St Paul’s Hospital, 1081 Burrard St, Providence Building Ward 6a, Vancouver, BC V6Z 1Y6, Canada (firstname.lastname@example.org).
Accepted for Publication: November 27, 2020.
Published Online: February 3, 2021. doi:10.1001/jamasurg.2020.6929
Author Contributions: Drs Gill and Clark had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Woodle and Gill contributed equally as co–first authors.
Concept and design: Woodle, Gill, First.
Acquisition, analysis, or interpretation of data: Woodle, Clark, Stewart, Alloway, First.
Drafting of the manuscript: Woodle, Gill, Clark, First.
Critical revision of the manuscript for important intellectual content: Woodle, Clark, Stewart, Alloway, First.
Statistical analysis: Clark, Stewart.
Obtained funding: Woodle.
Administrative, technical, or material support: Woodle, Stewart, Alloway, First.
Supervision: Woodle, Gill.
Conflict of Interest Disclosures: Dr Woodle reports grants from Astellas Pharma and grants and personal fees from Sanofi during the conduct of the study. Dr Gill reports grants and personal fees from Astellas Pharma outside the submitted work. Dr Alloway reports grants from Astellas Pharma during the conduct of the study. No other disclosures were reported.
Funding/Support: Dr Gill is supported by a foundation grant from the Canadian Institutes of Health Research.
Role of the Funder/Sponsor: The funding organization and original trial sponsor (Astellas) had on role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Disclaimer: The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as official policy of the US government.
Additional Contributions: We wish to acknowledge the original trial sponsor, Astellas Pharma, who supported the original trial by making the original trial data set available, the transplant centers that participated in the original trial, and Aparna Sadavarte, MS, at United Network of Organ Sharing who identified the trial participants in the Organ Procurement and Transplant Network registry. No compensation was received outside their standard salary.
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