Study shows withdrawal of corticosteroids does not impact graft survival
BOSTON — Patients randomized to early withdrawal of corticosteroids after a living or deceased donor transplant had near-identical outcomes to patients who continued corticosteroids, according to a study presented here.
“Maintenance steroids can be safely discontinued in patients treated with tacrolimus and mycophenolate with no difference in clinical outcomes with follow-up of greater than 15 years,” E. Steve Woodle, MD, of the University of Cincinnati College of Medicine, said. He presented the study results along with colleagues from Providence Health Care in Vancouver, B.C., Canada; the United Network for Organ Sharing, the source of the follow-up registry data, Transplant Genomics Inc., Yale University and the Split Rock Group.
Reduce side effects of steroids
The transplant community has long recognized the toxicity of steroids when added to the immunosuppressive drug regimen for patients with an organ transplant, Woodle said. Earlier efforts with smaller trials by transplant pioneer Thomas Starzl and others proved successful in safely eliminating steroids without jeopardizing the allograft, Woodle noted.
After tacrolimus and mycophenolate had received FDA approval for reducing the risk of allograft rejection, Astellas Pharmaceuticals launched the double-blind randomized controlled trial in 1999 to compare outcomes among patients who had early corticosteroid withdrawal (CSWD) and long-term corticosteroid therapy continuation (CCS) post-transplant.
“The purpose of the study was to evaluate long-term outcomes among participants in the original multicenter, randomized controlled clinical trial initiated in 1999 to demonstrate the use and limitations of UNOS/OPTN data in ascertaining long-term outcomes in RCT participants,” Woodle and the researchers wrote in their abstract.
Astellas Pharmaceuticals provided the original study data file that contained identifying data for participants. UNOS used a multi-step process to link participants to UNOS/OPTN data.
Patients were followed for 15 years using data from the UNOS files; outcomes could be determined in 385/386 study participants, including all 196 of the patients randomized to corticosteroid withdrawal at 7 days after transplantation and of 191 of the 192 patients randomized to continue the drug therapy.
Results showed time to allograft failure from any cause including death, death-censored allograft failure and death with allograft function were similar in patients randomized to CSWD or CCS.
“After 15 years, the [Modification of Diet in Renal Disease] MDRD estimated GFR was 55.7± 24 ml/min/1.73m2 in CSWD and 55.3 ± 27.2 ml/min/1.73m2 in the CCS groups with similar results in (per protocol) analyses,” according to the abstract.
The results were consistent among African American and non-African American participants, and among living and deceased donor recipients.
“The UNOS registry can be successfully utilized to obtain long-term RCT outcomes and this capacity should be expanded to promote future trials in transplantation,” the authors wrote. –by Mark E. Neumann
Woodle S, et al. Abstract #202. Presented at the 2019 American Transplant Congress. June 1-4, 2019; Boston.
Disclosures: Healio/Nephrology was unable to determine relevant financial disclosures prior to publication.