The adverse effects of corticosteroids have underscored a need to eliminate the drug from treatment regimens.
E. Steve Woodle, MD
A study found that corticosteroid withdrawal among low– to moderate–immune risk kidney transplant recipients was associated with long-term safety.
“Kidney transplant recipients require ongoing immunosuppressive drug treatment to prevent rejection. The most common immunosuppressive drug regimen includes 3 drugs, a calcineurin inhibitor (cyclosporine or tacrolimus), mycophenolic acid or azathioprine, and corticosteroids (i.e., prednisone),” wrote the study investigators.
Nevertheless, the adverse effects of corticosteroids have long been of concern and reason to attempt elimination of the drug from treatment regimens.
Therefore, the study, led by E. Steve Woodle, MD, College of Medicine, University of Cincinnati, Ohio, evaluated a prospective, multicenter, randomized double-blind placebo-controlled trial in order to compare long-term outcomes in patients who continued or withdrew from corticosteroid use in their post-operative regimen.
Corticosteroid Continuation Versus Cessation
The trial was conducted between November 1999-December 2002, and analysis occurred between 2018-June 2019.
The study consisted of 28 kidney transplant centers in the United States and included 386 low- to moderate-immune risk adult recipients.
Recipients also had no delayed graft function or short-term rejection in the first week post-transplant.
At baseline, patients were randomized 1:1 to receive tacrolimus and mycophenolate mofetil with or without corticosteroids 7 days after transplant.
The main outcomes sought by Woodle and colleagues were kidney allograft failure from any cause (including death) as well as allograft failure censored for patient death, which the investigators defined according to the requirement for long-term dialysis or repeat transplant.
The mean age of the trial population was 46.5 years, and median follow-up time was 15.8 years.
As such, results demonstrated there was minimal to no overall difference in outcomes between treatment groups.
For example, the hazard ratio of allograft failure from any cause was 0.83 (95% CI, 0.62-1.10; P = .19); the hazard ratio for allograft failure censored for patient death was 0.78 (95% CI, 0.52-1.19); P = .25).
The time to allograft failure from any cause and censored for death were not different between the groups. Similarly, there were no observed differences in the time to death at any time after transplant (P = .65) and time to death censored at time of allograft failure (P - .41).
These results were consistent with an analysis among the 223 patients who continued trial-assigned treatment of corticosteroid withdrawal (n = 114) or corticosteroids (n = 109) through at minimum of 5 years post-transplant.
The investigators further compared the outcomes of the trial participants with contemporary patients in the Organ Procurement and Transplant Network (OPTN) registry who likely would have been eligible for the trial and received similar immunosuppressive treatment.
“In a multivariable analysis including trial participants and registry patients, corticosteroid withdrawal was not associated with an increased risk of graft loss, trial participants had a similar hazard for graft loss as registry patients, and the association of corticosteroid withdrawal with allograft failure did not differ between trial participants and registry patients,” they wrote.
“Although these findings are reassuring, they are based on observational data and may be subject to residual confounding,” qualified the investigators.
They also acknowledged they were unable to determine long-term differences in nonfatal outcomes such as cardiovascular disease, diabetes, infections and metabolic bone disease.
The study, “Early Corticosteroid Cessation vs Long-term Corticosteroid Therapy in Kidney Transplant Recipients: Long-term Outcomes of a Randomized Clinical Trial,” was published online in JAMA Surgery.