Early Corticosteroid Cessation vs Long-term Corticosteroid Therapy in Kidney Transplant Recipients

Abstract

IMPORTANCEThe 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of corticosteroids is associated with a higher risk of short-term rejection, and the long-term outcomes of patients withdrawn from corticosteroids remain uncertain. OBJECTIVE 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. INTERVENTIONS 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. RESULTS 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.

Consensus recommendations for use of maintenance immunosuppression in solid organ transplantation: Endorsed by the American College of Clinical Pharmacy, American Society of Transplantation, and the International Society for Heart and Lung Transplantation

“…Long-term similar patient and allograft survival were confirmed in a follow-up analysis of a landmark study. 218 The adjusted hazard ratios of all-cause and death-censored allograft failure in those assigned to withdraw from steroids were 0.83, 95% CI 0.62-1.10, p = 0.19 and 0.78, 95% CI, 0.52-1.19, p = 0.25; and did not differ between groups. Corticosteroid withdrawal has also been associated with improvement in metabolic endpoints such as hyperlipidemia, serum triglycerides, need for insulin to treat diabetes, and changes in HgA1c.…”

“…Corticosteroid withdrawal has been successfully done in low and moderate risk kidney transplant recipients, but may result in higher incidence of BPAR with similar patient and allograft survival 195–217 . Long‐term similar patient and allograft survival were confirmed in a follow‐up analysis of a landmark study 218 . The adjusted hazard ratios of all‐cause and death‐censored allograft failure in those assigned to withdraw from steroids were 0.83, 95% CI 0.62–1.10, p = 0.19 and 0.78, 95% CI, 0.52–1.19, p = 0.25; and did not differ between groups.…”

Effect of Early Steroid Withdrawal on Posttransplant Diabetes Among Kidney Transplant Recipients Differs by Recipient Age

“…Previous research supported that renal function 39 and graft survival 22 among recipients with ESW is comparable with among those with CSM. A randomized clinical trial data by Woodle et al 40 observed no difference of long-term death-censored graft failure and all-cause graft failure between ESW and CSM.…”

Steroid avoidance/withdrawal and maintenance immunosuppression in pediatric kidney transplantation

“…Patients were on Tac and MMF for maintenance immunosuppression. The study found no difference in PS (0.83; 95% CI, 0.62–1.10; p = .19) and death‐censored GS (0.78; 95% CI 0.52–1.19; p = .25) over a median follow‐up of 15.8 years 19 …”