Early Corticosteroid Cessation vs Long-term Corticosteroid Therapy in Kidney Transplant Recipients: Long-term Outcomes of a Randomized Clinical Trial.

Importance: 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of corticosteroids is associated with a higher risk of short-term rejection, and the long-term outcomes of patients withdrawn from corticosteroids remain uncertain.

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.