May 20, 2004 (Boston) — Preliminary results of a five-year prospective, randomized, controlled, double-blinded study shows it may be possible to withdraw corticosteroids during the first week posttransplant, without increasing rejection in de novo kidney transplant patients, researchers reported here Tuesday.

E. Steven Woodle, MD, from the University of Cincinnati in Ohio, presented results on behalf of the 26 centers participating in the Fujisawa Steroid Withdrawal Study Group at the 2004 American Transplant Congress, the joint meeting of the American Society of Transplant Surgeons and the American Society of Transplantation.

Fujisawa is funding the trial, which aims to show if steroids can be safely withdrawn from African-American recipients, Dr. Woodle told Medscape in an interview.

Session moderator Sandy Feng, MD, an assistant professor of medicine at the University of California in San Francisco, said the exclusion criteria — barring patients at highest risk for rejection, such as those with delayed graft function — could end up providing results that are meaningless to most transplant recipients.

But Dr. Woodle disagreed, stating that he believes the results will apply to all first-time cadaveric recipients and African Americans, which he estimated at 75% of the transplant population.

Patients with peak percent reactive antibody (PRA) of more than 50% or current PRA of more than 25% were not enrolled. The mean age was 46.4, and a majority (66%) of patients were men and white (67%), while 20% were African American. Forty-three percent of recipients received a cadaveric organ.

Dr. Woodle said that the study is the largest and the first randomized controlled trial that attempts to show whether steroid withdrawal is feasible with modern immunosuppressive agents.

Several previous studies have been in patients taking older therapies, and have erroneously suggested that steroid withdrawal would lead to late graft loss, Dr. Woodle said.

The study is fully enrolled and due to run another two years (the follow-up period reported at the meeting was 18 months). But if results continue to be positive, the investigators are considering removing the blinds before the five-year mark, said Dr. Woodle, adding that three years of data should be sufficient to draw initial conclusions.

In the trial, 386 patients were randomized to corticosteroid withdrawal seven days posttransplant, or to long-term steroid use (5 mg daily). All were given an interleukin-2R antibody or thymoglobulin for induction, followed by tacrolimus (target, 10-20 ng/mL from day 1-90, and 5-15 mg/mL thereafter) and mycophenolate mofetil (2 g/day).

The primary end point was treatment failure, a composite including death, graft loss, or severe acute rejection at six months, one year, and each year thereafter until the study's completion. Secondary end points were rejection severity; proportion of patients needing antilymphocyte therapy for acute rejection; patient and graft survival; incidence of posttransplant diabetes and infection; change in Framingham Heart Study Coronary Heart Disease Risk point total; incidence and severity of hypercholesterolemia and hypertriglyceridemia; treatment, incidence, and severity of hypertension; incidence of posttransplant malignancies and leukopenia; cumulative steroid dose; and patient weight change.

At one year, 96% of patients survived with a functioning graft, and the biopsy-confirmed acute rejection rate was 10.4%. Three quarters of the episodes were mild, said Dr. Woodle. Overall, posttransplant diabetes incidence was 5%, triglycerides and other lipid measures were lower, and the Framingham Global Risk score dropped from 8.4% at baseline to 7.6%, he said.

"With these positive year 1 initial results, we are well on our way to achieving the study's objective,"said Dr. Woodle.

ATC 2004: Abstract 1528. Presented May 18, 2004.

Reviewed by Gary D. Vogin, MD