CHICAGO — For kidney transplant patients at low immunologic risk, chronic corticosteroid therapy can be rapidly withdrawn after induction therapy with either basiliximab or rabbit anti-thymocyte globulin (AGT), results from the 12-month HARMONY study show.
“We thought that maybe basiliximab would not be as strong an immunosuppressant as the rabbit AGT regimen, but this was not the case. They were equivalent,” said Christian Hugo, MD, from the University of Dresden in Germany. “This was surprising to us.”
And the added benefit was a marked reduction in the development in post-transplant diabetes mellitus in the first year after transplantation,” he reported.
Dr Hugo presented findings from the multicenter randomized controlled HARMONY study here at Kidney Week 2016; the results were published online simultaneously in the Lancet.
After kidney transplantation, about one-third of the patients received induction therapy with basiliximab plus the gold-standard immunosuppressive regimen established in the SYMPHONY trial about a decade ago: the combination of low-dose tacrolimus, mycophenolate mofetil, and oral corticosteroids.
About one-third received induction therapy with basiliximab plus the immunosuppressive regimen, but corticosteroids were withdrawn 8 days after transplantation.
And about one-third received induction therapy with rabbit ATG plus the immunosuppressive regimen, but corticosteroids were withdrawn 8 days after transplantation.
There was no difference in the primary end point — biopsy-proven rejection rate at 12 months — between the three treatment groups, or in the safety parameters.
At the 12-month evaluation point, patient and graft survival were “excellent and equivalent” in all groups, Dr Hugo reported.
Table. 12-Month Outcomes in the HARMONY StudyTreatment GroupBiopsy-Proven Acute Rejection, %Post-Transplant Diabetes, %Graft Survival, %Continuous steroid use11.239.296.1Rapid steroid withdrawal after basiliximab induction therapy10.623.996.8Rapid steroid withdrawal after rabbit AGT induction therapy9.922.795.8
In the year after transplantation, diabetes mellitus developed in patients who experienced the rapid withdrawal of steroids at almost half the rate of those who continued on maintenance steroids (P = .007), Dr Hugo explained.
This finding is not inconsequential, he pointed out. Many studies have shown an association between survival and the development of diabetes after transplantation over the long term.
One such study showed that new-onset diabetes was not associated with graft loss, but was associated with an increased risk for death with a functioning graft over long-term follow-up (Clin J Am Soc Nephrol. 2008;3:814-821).
However, Dr Hugo stressed that the rapid withdrawal of steroids after transplantation is only safe and feasible for patients at low immunologic risk for rejection.
“This was a German study, so virtually all patients were Caucasian, 95% were first transplant patients, and 90% of patients had no plasma reactive antibodies, so they were not sensitized before we started with the trial,” Dr Hugo explained. In addition, “we had a very short cold ischemia time.”
“Those are all circumstances that make up a low-immunological-risk patient,” he added.
“My take-home message is, at least for low-immunological-risk patients, HARMONY may be better than SYMPHONY,” Dr Hugo said.
“Our transplant patients are living longer and longer, so they are getting comorbid conditions, including diabetes, infections, and cancers,” said Gretchen Brandt, MD, from Kaiser Permanente in Washington, DC, who was not involved in the study. “We want them to have a good quality of life and not get these complications.”
“Post-transplant diabetes is so difficult to manage downstream for nephrologists,” she told Medscape Medical News. “It’s nice to be able to think about them becoming steroid ‘free-ish’.”
The study was funded by Astellas Pharma, Sanofi, and Roche Pharma. Dr Hugo reports financial relationships with Astellas, Novartis, Roche, BMS, Pfizer, Boehringer Ingelheim and Amgen.
Kidney Week 2016: American Society of Nephrology Annual Meeting: Abstract HI-OR03. Presented November 19, 2016.
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